<strong>Objective:</strong> To explore the close relationship between respiratory syncytial virus (RSV) infection and acute attack of childhood asthma. <strong>Methods:</strong> A computer-base...<strong>Objective:</strong> To explore the close relationship between respiratory syncytial virus (RSV) infection and acute attack of childhood asthma. <strong>Methods:</strong> A computer-based search of database from Pumbed, CNKI, Wanfang, Baidu Scholar, Chongqing VIP, GeenMedica was performed to screen the articles about respiratory syncytial virus infection and childhood asthma. Then the literatures were screened out by the selection criteria. The RevMan5.3 software was used to test the heterogeneity and effect values of each study, analyze the sensitivity and publication bias of the literature, and draw on Meta forest plot and Funnel plot. <strong>Results:</strong> 5 articles conformed to the selection criteria. There were totally 881 cases in the case group, 826 cases in the control group. The results of heterogeneity test showed no heterogeneity between each study (P > 0.05). The fixed-effects model showed the 6.68 (5.06 - 8.82), (Z = 13.38, P < 0.00001). <strong>Conclusion:</strong> The infection rate of respiratory syncytial virus in children with acute asthma attack is higher than that in remission period. Respiratory syncytial virus infection rate can be used as an indicator of the severity of asthma in children.展开更多
Introduction: Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. Objective: To characterize the cytokine response in RSV+ infants aged 0 -...Introduction: Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. Objective: To characterize the cytokine response in RSV+ infants aged 0 - 36 months and to relate their responses to disease severity. Methods: Nasopharyngeal aspirations (NPAs) were analyzed for RSV and IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-1RA, IL-4R, IFN-γ, sTNFR1, sTNFR2, and TNF-α. Clinical data were collected from the medical records. Results: We included 331 infants of whom 214 were RSV+. In comparison to RSV- infants, they had significantly higher levels of TNF-α, IL-6, IL-1β, and IFN-γ (p α, IL-6, and IL-1β. sTNFR1/2 were significantly increased in RSV+ infants. Hospitalized patients had significantly higher levels of TNF-α, sTNFR2, and IL-10 (p < 0.05) than non-hospitalized patients. The cytokine response could not be related to disease severity. We found no evidence of a skewed Th1/Th2 immune profile. Conclusion: In acute RSV disease, infected infants’ NPAs contain a significant amount of pro-inflammatory cytokines. Whether this response is beneficial or deleterious remains unanswered. Interpersonal variations in cytokine responses might be linked to an inherited tendency to variations in disease severity.展开更多
Objective:Qingfei oral liquid(QF),an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction,has ...Objective:Qingfei oral liquid(QF),an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction,has been effectively used since decades to treat patients with viral pneumonia and asthma.In our previous study,we had demonstrated that QF can significantly reduce airway hyperresponsiveness,hyperemia,lung tissue edema,inflammatory lung tissue infiltration in mice,airway mucus secretion,and peripheral airway collagen hyperplasia;however,its mechanism of action is unknown.Methods:Fifty 6–8-week-old male BALB/c mice were equally and randomly divided into five groups:the control,ovalbumin(OVA),OVA+respiratory syncytial virus(RSV),QF,and dexamethasone(Dxms)groups.The QF group was administered QF at 1.17 g·kg−1·d−1,the Dxms group received dexamethasone injections at 0.2 mg·kg−1·d−1,and the remaining groups were administered PBS.Inflammation in the lung tissue was assessed by hematoxylin and eosin(HE),periodic acid–Schiff(PAS),and Van Gieson staining.ELISA was used to evaluate the IL-13,IL-25,and IL-33 in the mice.Western blotting was used to examine changes in the proteins levels of transient receptor potential vanilloid-1(TRPV1)and mucin 5AC(MUC5AC)in the lung tissues of mice.Results:Histopathological evaluation revealed that the OVA and OVA+RSV groups exhibited lung tissue edema and inflammatory lung tissue infiltration in the HE staining and airway secretions in the PAS staining;collagen hyperplasia around the airway was increased in these two groups compared with the control group.The QF group exhibited significantly reduced lung tissue edema,inflammatory lung tissue infiltration,airway secretions,and collagen hyperplasia around the airway compared with the OVA+RSV group.We analyzed the serum levels of IL-13,IL-25,and IL-33 in the mice and found that these levels were higher in the OVA and OVA+RSV groups than in the control group(P<0.05 in the OVA group,P<0.01 in the OVA+RSV group).The QF group exhibited significantly decreased serum levels of IL-13,IL-25,and IL-33 compared with the OVA+RSV group(all P<0.05).The Dxms group also exhibited significant decreases in the serum levels of IL-13 and IL-33(all P<0.05)but no significant decrease in the serum levels of IL-25 compared with the RSV+OVA group.Finally,we examined the protein levels of TRPV1 and MUC5AC in the lung tissues of mice using Western blotting.After identifying RSV infection in the mice with asthma,the protein levels of TRPV1 and MUC5AC in the lung tissues of mice were significantly higher than those in the control group(P<0.05,P<0.01).We found that compared with RSV+OVA,QF can significantly downregulate the protein level of TRPV1;further,the protein level of MUC5AC was also significantly reduced(all P<0.001).Conclusion:QF can inhibit RSV replication and reduce airway inflammation and mucus hypersecretion injury caused by RSV infection and asthma,and its mechanism of action may be associated with the downregulation of TRPV1 expression and a decrease in airway mucus hypersecretion injury.展开更多
Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea offici...Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.展开更多
Pediatric respiratory syncytial viral infection (RS) usually shows </span><span style="font-family:Verdana;">relatively</span><span style="font-family:Verdana;"> good </s...Pediatric respiratory syncytial viral infection (RS) usually shows </span><span style="font-family:Verdana;">relatively</span><span style="font-family:Verdana;"> good </span><span style="font-family:Verdana;">outcome</span><span style="font-family:Verdana;">;however, when it accompanies acute respiratory distress syndrome (ARDS), this becomes fatal. We experienced three pediatric patients with RS + ARDS, with all showing good </span><span style="font-family:Verdana;">outcome</span><span style="font-family:Verdana;"> with steroid pulse therapy. We wish to emphasize;1) steroid pulse therapy may become an option for this condition, and 2) plasma KL-6 and surfactant protein D levels may become a biomarker reflecting the disease progression/condition. Patients were, aged 1 month, 1 year 5 months, and 1 year 11 months. In all three, the respiratory condition deteriorated rapidly, requiring invasive ventilator management. Although the effectiveness of steroid treatment for ARDS is controversial, </span><span style="font-family:Verdana;">very</span><span style="font-family:Verdana;"> severe condition prompted us to employ steroid pulse therapy, after which, oxygenation rapidly improved without adverse events. Plasma KL-6 and surfactant protein D levels were measured during exacerbations of ARDS, steroid pulse therapy, and recovery. Surfactant protein D levels were closely associated with oxygenation, suggesting this substance level might be a biomarker of ARDS caused by the disruption of the alveolar epithelial lining and to understand oxygenation without time lag.展开更多
Objective Fusion protein is a subunit of the human respiratory syncytial virus(HRSV)and a potential vaccine candidate.Thus,a study on the genetic characteristics of F protein was considered important for further inves...Objective Fusion protein is a subunit of the human respiratory syncytial virus(HRSV)and a potential vaccine candidate.Thus,a study on the genetic characteristics of F protein was considered important for further investigations in this field.The aim of this study was to determine the prevalence and genetic diversity of the F gene of HRSV infections in hospitalized pediatric patients in Beijing with acute lower respiratory tract infections and to compare the circulating genotypes that are currently found worldwide.Methods HRSV particles were amplified by RT-PCR and the PCR products were purified for sequencing.Further analysis was carried out by Bioedit and MEGA 3.0 biological software programs.Results Seventy-six samples(23.1%)were positive for HRSV.The percentage of cases in patients younger than 1year was 84.21%.Among the six Beijing isolates,four belonged to subgroup A,whose respective F genes shared97.0%-97.4%nucleotide sequence identity and 92.1%-93.0%amino acid sequence identity.The other two isolates belonged to subgroup B.Here,97.3%and 98.2%sequence identity were found at nucleotide and amino acid levels,respectively.Conclusions Phylogenetic analysis of nucleotide sequences revealed that those four isolates within subgroup A were monophyletic and closely related to each other,but those two within subgroup B distributed in two distinct clusters.Subgroup A and B strains co-circulated,indicating that two different transmission chains occurred in Beijing from 2003-2004.展开更多
Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5...Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years,representing a major global healthcare burden.There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life.A multidisciplinary consensus development group comprising experts in epidemiology,infectious diseases,respiratory medicine,and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.Data sources The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Library,using variations in terms for"respiratory syncytial virus","RSV","lower respiratory tract infection","bronchiolitis","acute","viral pneumonia","neonatal","infant""children",and"pediatric".Results Evidence-based recommendations regarding diagnosis,treatment,and prevention were proposed with a high degree of consensus.Although supportive care remains the cornerstone for the management of RSV infections,new monoclonal antibodies,vaccines,drug therapies,and viral surveillance techniques are being rolled out.Conclusions This consensus,based on international and national scientific evidence,reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections.Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.展开更多
Background Respiratory syncytial virus(RSV)infection in infants is a global health priority.We aimed to investigate the common manifestations of RSV infection by age group and human development index(HDI)level and to ...Background Respiratory syncytial virus(RSV)infection in infants is a global health priority.We aimed to investigate the common manifestations of RSV infection by age group and human development index(HDI)level and to assess its association with the development of wheezing and recurrent wheezing illness.Methods We searched the literature published between January 1,2010 and June 2,2022 in seven databases.Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children.Random-and fixed-effect models were used to estimate the effect size and their 95%confidence intervals.Subgroup analysis was conducted by age and HDI levels.This review was registered in PROSPERO(CRD42022379401).Results The meta-analysis included 47 studies.The top five manifestations were cough(92%),nasal congestion(58%),rhinorrhea(53%),shortness of breath(50%),and dyspnea(47%).The clinical symptoms were most severe in infants.In our analysis,compared to very high and high HDI countries,fewer studies in medium HDI countries reported related manifestations,and no study in low HDI countries reported that.The RSV-infected infants were more likely to develop wheezing than the non-infected infants[odds ratio(OR),3.12;95%CI,2.59–3.76]and had a higher risk of developing wheezing illnesses after recovery(OR,2.60;95%CI,2.51–2.70).Conclusions Cough and shortness of breath are common manifestations of RSV infection.More attention should be given to infants and areas with low HDI levels.The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.展开更多
Respiratory syncytial virus(RSV)is the most common cause of viral bronchiolitis among children worldwide,yet there is no vaccine for RSV disease.This study investigates the potential of cube and sphere-shaped cerium o...Respiratory syncytial virus(RSV)is the most common cause of viral bronchiolitis among children worldwide,yet there is no vaccine for RSV disease.This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles(CNP)to modulate reactive oxygen(ROS)and nitrogen(RNS)species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo.Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods,respectively.Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential.In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages.Specifically,cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels.Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFαand IL-12p70,while simultaneously decreasing M2 CD206 expression.Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice.Notably,cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation,avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils,which are associated with RSV-mediated inflammation.In conclusion,we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection.展开更多
Human respiratory syncytial virus(RSV)is a severe threat to children and a main cause of acute lower respiratory tract infections.Nevertheless,the intra-host evolution and inter-regional diffusion of RSV are little kn...Human respiratory syncytial virus(RSV)is a severe threat to children and a main cause of acute lower respiratory tract infections.Nevertheless,the intra-host evolution and inter-regional diffusion of RSV are little known.In this study,we performed a systematic surveillance in hospitalized children in Hubei during 2020–2021,in which 106 RSV-positive samples were detected both clinically and by metagenomic next generation sequencing(mNGS).RSV-A and RSV-B groups co-circulated during surveillance with RSV-B being predominant.About 46 high-quality genomes were used for further analyses.A total of 163 intra-host nucleotide variation(iSNV)sites distributed in 34 samples were detected,and glycoprotein(G)gene was the most enriched gene for iSNVs,with non-synonymous substitutions more than synonymous substitutions.Evolutionary dynamic analysis showed that the evolutionary rates of G and NS2 genes were higher,and the population size of RSV groups changed over time.We also found evidences of inter-regional diffusion from Europe and Oceania to Hubei for RSV-A and RSV-B,respectively.This study highlighted the intra-host and inter-host evolution of RSV,and provided some evi-dences for understanding the evolution of RSV.展开更多
Background:The influence of Mycoplasma pneumoniae(MP)infection on bronchiolitis remains unclear.Additionally,reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been in...Background:The influence of Mycoplasma pneumoniae(MP)infection on bronchiolitis remains unclear.Additionally,reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been inconclusive.Methods:Children with respiratory syncytial virus(RSV)-induced bronchiolitis were divided into two groups:RSV+MP group and RSV group.Each group was randomly divided into two subgroups:one received routine and placebo treatment,while the other received routine and montelukast treatment for 9 months.The cumulative numbers of wheezing episodes and recurrent respiratory tract infections were recorded.Blood parameters were determined.Results:Patients in the RSV+MP group exhibited an older average age,fever,more frequent flaky and patchy shadows in chest X-rays,more frequent extrapulmonary manifestations,and longer hospital stays compared with patients in the RSV group.Additionally,higher baseline blood eosinophil counts,eosinophil cationic protein(ECP),total immunoglobulin E(IgE),interleukin(IL)-4,IL-5,IL-4/interferon-γratios,leukotriene(LT)B4,and LTC4,and lower baseline lipoxin A4(LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the RSV group.Montelukast treatment decreased the cumulative numbers of recurrent wheezing episodes and recurrent respiratory tract infections at 9 and 12 months.This efficacy may be related to the montelukast-induced reductions in peripheral eosinophil counts,ECP and total IgE,as well as the montelukast-dependent recovery in T helper(Th)1/Th2 balance and LXA4/LTB4 ratios in children with bronchiolitis.Conclusions:RSV bronchiolitis with MP infection was associated with clinical and laboratory features that differed from those of RSV bronchiolitis without MP infection.Add-on therapy with montelukast for 9 months was benefi cial for children with bronchiolitis at 9 and 12 months after the initiation of treatment.展开更多
Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated re...Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice.The constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain(A2cpts)or further combined with SH gene deletion(A2cptsΔSH),HDV ribozyme(δ),and a T7 terminator.These vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2-1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero cells.The rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2cp,rRSV-Long/A2cpts,and rRSV-Long/A2cptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or deletion.Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in vivo.Furthermore,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory disease.We showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of rRSV.By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.展开更多
Accurate diagnosis of early infections caused by the viral pathogen is a major challenge because patients usually have nonspecific signs.The development of sensitive,reliable,robust,and rapid laboratory tools is still...Accurate diagnosis of early infections caused by the viral pathogen is a major challenge because patients usually have nonspecific signs.The development of sensitive,reliable,robust,and rapid laboratory tools is still in high demand.Herein,we developed an extremely sensitive and affordable plasmonic immunoassay for respiratory syncytial virus(RSV)detection with the naked eye based on gold nanoparticles(AuNPs)/graphene hybrids combined with metal enhancement solution.The limit of detection was found to be 1.7 fg/mL,which was 100 times higher than that of the AuNPs-based method.The ultrahigh sensitivity could be attributed to the large number of well-dispersed AuNPs deposited on the graphene surface,which had an extremely high relative surface area.Further signal amplification was achieved by catalytic enlargement of AuNPs with HAuCl_(4)-NH_(2)OH redox reaction.Moreover,the plasmonic immunoassay was successfully used to detect RSV in artificial serum samples,showing great potential in practical applications.展开更多
Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a mol...Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.展开更多
Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature s...Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature search including EMBASE,MEDLINE,and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant,prematurity,and BPD between 1980 and 2014.Results:Recurrent respiratory symptoms remain common at preschool age,school age and even into young adulthood.Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the fi rst years of life.Infl uenza virus infection plays a minor role compared to respiratory syncytial virus(RSV)associated respiratory tract infection during infancy and early childhood.Nevertheless,particular morbidity to both viruses is high.Conclusions:The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the fi rst two years of life.Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months,and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.展开更多
Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world...Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.展开更多
Respiratory syncytial virus(RSV) is the major cause of lower respiratory tract infections in children. Inactivated RSV vaccine was developed in the late 1960’s, but the vaccine-enhanced disease(VED) occurred to vacci...Respiratory syncytial virus(RSV) is the major cause of lower respiratory tract infections in children. Inactivated RSV vaccine was developed in the late 1960’s, but the vaccine-enhanced disease(VED) occurred to vaccinated infants upon subsequent natural RSV infection. The excessive inflammatory immunopathology in the lungs might be involved in the VED, but the underlying mechanisms remain not fully understood. In this study, we utilized UV-inactivated RSV in the prime/boost approach followed by RSV challenge in BALB/c mice to mimic RSV VED. The dynamic virus load,cytokines, histology and transcriptome profiles in lung tissues of mice were investigated from day 1 to day 6 post-infection.Compared to PBS-treated mice, UV-RSV vaccination leads to a Th2 type inflammatory response characterized by enhanced histopathology, reduced Treg cells and increased IL4^(+)CD4 T cells in the lung. Enhanced production of several Th2 type cytokines(IL-4, IL-5, IL-10) and TGF-b, reduction of IL-6 and IL-17 were observed in UV-RSV vaccinated mice. A total of 5582 differentially expressed(DE) genes between PBS-treated or vaccinated mice and na?ve mice were identified by RNA-Seq. Eleven conserved high-influential modules(HMs) were recognized, majorly grouped into regulatory networks related to cell cycle and cell metabolism, signal transduction, immune and inflammatory responses. At an early time post-infection, the vaccinated mice showed obvious decreased expression patterns of DE genes in 11 HMs compared to PBS-treated mice. The extracellular matrix(HM5) and immune responses(HM8) revealed tremendous differences in expression and regulation characteristics of transcripts between PBS-treated and vaccinated mice at both early and late time points. The highly connected genes in HM5 and HM8 networks were further validated by RT-qPCR.These findings reveal the relationship between RSV VED and immune responses, which could benefit the development of novel RSV vaccines.展开更多
Background:To investigate the clinical characteristics and analyze risk factors for severe respiratory syncytial virus(RSV)infection in hospitalized infants with acute lower respiratory tract infections(ALRIs).Methods...Background:To investigate the clinical characteristics and analyze risk factors for severe respiratory syncytial virus(RSV)infection in hospitalized infants with acute lower respiratory tract infections(ALRIs).Methods:A retrospective review of the medical records of infants with RSV-associated ALRIs between March 1st,2011 and February 29th,2012 was conducted.Subjects were followed up over the phone or by outpatient visit six and twelve months after discharge.Results:Among 913 RSV-associated ALRIs infants,288(31.5%)had severe infections,which accounted for 4.2%of hospitalized children.The hospital RSV mortality rate was 1.0%.The proportions of cases with tachypnea,apnea,cyanosis,and fine rales were significantly higher in the severe ALRIs group(all P<0.001).Multivariate logistic regression showed that low-birth-weight[1.698(1.028-2.805)],age less than 3 months old[3.385(2.174-5.271)],congenital heart disease[1.667(1.149-2.418)],bronchopulmonary dysplasia[8.505(1.731-41.780)],and airway abnormalities[2.246(1.008-5.005)]were independent risk factors for severe ALRIs.The incidence of bronchitis,pneumonia and readmission in the severe group was significantly higher than that of the non-severe group during the one-year follow-up(all P<0.001).Conclusions:Younger age,low birth weight and underlying disease are associated with severe RSVassociated ALRIs.Furthermore,severe RSV infections may be associated with a higher frequency of subsequent bronchitis,pneumonia and re-hospitalization in the following year.展开更多
Respiratory Syncytial Viral Infection is one of the most common viral infections in the respiratory airways and is more common in infants, younger children and some adults. Although ribavirin has been used in the mana...Respiratory Syncytial Viral Infection is one of the most common viral infections in the respiratory airways and is more common in infants, younger children and some adults. Although ribavirin has been used in the management of RSV infection, many effective drugs are still under development. Also, structured based drug design using computational tools has shifted the paradigm of drug design and discovery. The fusion core of the Respiratory Syncytial Viral (RSV) structure is crucial for its fusion, entry and replication in the host cell. Herein, we investigated the interruption of the formation and/or the stability of the fusion core. 15 ligands were screened and 4 (Glimepiride, Glipizide, Canagloflozin, Glibenclamide) of them are potential drug candidate for experimental validation, preclinical trials, clinical trials and route of administration optimization. To the best of our knowledge, this is the first time of reporting lead molecules against RSV from oral hypoglycemic agents. It also suggests the ligands for consideration as prophylactics in infants and adults via the inhalation route.展开更多
Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prev...Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.展开更多
文摘<strong>Objective:</strong> To explore the close relationship between respiratory syncytial virus (RSV) infection and acute attack of childhood asthma. <strong>Methods:</strong> A computer-based search of database from Pumbed, CNKI, Wanfang, Baidu Scholar, Chongqing VIP, GeenMedica was performed to screen the articles about respiratory syncytial virus infection and childhood asthma. Then the literatures were screened out by the selection criteria. The RevMan5.3 software was used to test the heterogeneity and effect values of each study, analyze the sensitivity and publication bias of the literature, and draw on Meta forest plot and Funnel plot. <strong>Results:</strong> 5 articles conformed to the selection criteria. There were totally 881 cases in the case group, 826 cases in the control group. The results of heterogeneity test showed no heterogeneity between each study (P > 0.05). The fixed-effects model showed the 6.68 (5.06 - 8.82), (Z = 13.38, P < 0.00001). <strong>Conclusion:</strong> The infection rate of respiratory syncytial virus in children with acute asthma attack is higher than that in remission period. Respiratory syncytial virus infection rate can be used as an indicator of the severity of asthma in children.
基金Funding has been granted from the Medical Research Foundation in Region III,East-Danish Medical Research Forum(ΦSFF)Frederiks-borg County Research Foundation+5 种基金Rosalie Petersen’s FoundationCaptain Harald Jensen and Wife’s FoundationMrs Olga Bryde Nielsen’s FoundationTvergaard Foundationthe Danish Medical Association’s Research Foundationthe Danish Pediatric Society(DPS).
文摘Introduction: Variability in severity of Respiratory Syncytial Virus (RSV) infection is reportedly due to differences in inflammatory response. Objective: To characterize the cytokine response in RSV+ infants aged 0 - 36 months and to relate their responses to disease severity. Methods: Nasopharyngeal aspirations (NPAs) were analyzed for RSV and IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-1RA, IL-4R, IFN-γ, sTNFR1, sTNFR2, and TNF-α. Clinical data were collected from the medical records. Results: We included 331 infants of whom 214 were RSV+. In comparison to RSV- infants, they had significantly higher levels of TNF-α, IL-6, IL-1β, and IFN-γ (p α, IL-6, and IL-1β. sTNFR1/2 were significantly increased in RSV+ infants. Hospitalized patients had significantly higher levels of TNF-α, sTNFR2, and IL-10 (p < 0.05) than non-hospitalized patients. The cytokine response could not be related to disease severity. We found no evidence of a skewed Th1/Th2 immune profile. Conclusion: In acute RSV disease, infected infants’ NPAs contain a significant amount of pro-inflammatory cytokines. Whether this response is beneficial or deleterious remains unanswered. Interpersonal variations in cytokine responses might be linked to an inherited tendency to variations in disease severity.
基金This work was supported by Natural Science Foundation of China(81674020).
文摘Objective:Qingfei oral liquid(QF),an experimental Chinese medicine prescription developed from the ancient priscription of traditional Chinese medicines Ma Xin Shi Gan decoction and Tingli Dazao Xie Fei decoction,has been effectively used since decades to treat patients with viral pneumonia and asthma.In our previous study,we had demonstrated that QF can significantly reduce airway hyperresponsiveness,hyperemia,lung tissue edema,inflammatory lung tissue infiltration in mice,airway mucus secretion,and peripheral airway collagen hyperplasia;however,its mechanism of action is unknown.Methods:Fifty 6–8-week-old male BALB/c mice were equally and randomly divided into five groups:the control,ovalbumin(OVA),OVA+respiratory syncytial virus(RSV),QF,and dexamethasone(Dxms)groups.The QF group was administered QF at 1.17 g·kg−1·d−1,the Dxms group received dexamethasone injections at 0.2 mg·kg−1·d−1,and the remaining groups were administered PBS.Inflammation in the lung tissue was assessed by hematoxylin and eosin(HE),periodic acid–Schiff(PAS),and Van Gieson staining.ELISA was used to evaluate the IL-13,IL-25,and IL-33 in the mice.Western blotting was used to examine changes in the proteins levels of transient receptor potential vanilloid-1(TRPV1)and mucin 5AC(MUC5AC)in the lung tissues of mice.Results:Histopathological evaluation revealed that the OVA and OVA+RSV groups exhibited lung tissue edema and inflammatory lung tissue infiltration in the HE staining and airway secretions in the PAS staining;collagen hyperplasia around the airway was increased in these two groups compared with the control group.The QF group exhibited significantly reduced lung tissue edema,inflammatory lung tissue infiltration,airway secretions,and collagen hyperplasia around the airway compared with the OVA+RSV group.We analyzed the serum levels of IL-13,IL-25,and IL-33 in the mice and found that these levels were higher in the OVA and OVA+RSV groups than in the control group(P<0.05 in the OVA group,P<0.01 in the OVA+RSV group).The QF group exhibited significantly decreased serum levels of IL-13,IL-25,and IL-33 compared with the OVA+RSV group(all P<0.05).The Dxms group also exhibited significant decreases in the serum levels of IL-13 and IL-33(all P<0.05)but no significant decrease in the serum levels of IL-25 compared with the RSV+OVA group.Finally,we examined the protein levels of TRPV1 and MUC5AC in the lung tissues of mice using Western blotting.After identifying RSV infection in the mice with asthma,the protein levels of TRPV1 and MUC5AC in the lung tissues of mice were significantly higher than those in the control group(P<0.05,P<0.01).We found that compared with RSV+OVA,QF can significantly downregulate the protein level of TRPV1;further,the protein level of MUC5AC was also significantly reduced(all P<0.001).Conclusion:QF can inhibit RSV replication and reduce airway inflammation and mucus hypersecretion injury caused by RSV infection and asthma,and its mechanism of action may be associated with the downregulation of TRPV1 expression and a decrease in airway mucus hypersecretion injury.
基金Key Science and Technology Project of Hainan Province(No.ZDKJ202003)Hainan Provincial Natural Science Foundation of China(No.821QN262)+1 种基金Hainan Provincial Natural Science Foundation of China(No.2019RC207)Hainan Provincial Natural Science Foundation of China(No.820RC628)。
文摘Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.
文摘Pediatric respiratory syncytial viral infection (RS) usually shows </span><span style="font-family:Verdana;">relatively</span><span style="font-family:Verdana;"> good </span><span style="font-family:Verdana;">outcome</span><span style="font-family:Verdana;">;however, when it accompanies acute respiratory distress syndrome (ARDS), this becomes fatal. We experienced three pediatric patients with RS + ARDS, with all showing good </span><span style="font-family:Verdana;">outcome</span><span style="font-family:Verdana;"> with steroid pulse therapy. We wish to emphasize;1) steroid pulse therapy may become an option for this condition, and 2) plasma KL-6 and surfactant protein D levels may become a biomarker reflecting the disease progression/condition. Patients were, aged 1 month, 1 year 5 months, and 1 year 11 months. In all three, the respiratory condition deteriorated rapidly, requiring invasive ventilator management. Although the effectiveness of steroid treatment for ARDS is controversial, </span><span style="font-family:Verdana;">very</span><span style="font-family:Verdana;"> severe condition prompted us to employ steroid pulse therapy, after which, oxygenation rapidly improved without adverse events. Plasma KL-6 and surfactant protein D levels were measured during exacerbations of ARDS, steroid pulse therapy, and recovery. Surfactant protein D levels were closely associated with oxygenation, suggesting this substance level might be a biomarker of ARDS caused by the disruption of the alveolar epithelial lining and to understand oxygenation without time lag.
文摘Objective Fusion protein is a subunit of the human respiratory syncytial virus(HRSV)and a potential vaccine candidate.Thus,a study on the genetic characteristics of F protein was considered important for further investigations in this field.The aim of this study was to determine the prevalence and genetic diversity of the F gene of HRSV infections in hospitalized pediatric patients in Beijing with acute lower respiratory tract infections and to compare the circulating genotypes that are currently found worldwide.Methods HRSV particles were amplified by RT-PCR and the PCR products were purified for sequencing.Further analysis was carried out by Bioedit and MEGA 3.0 biological software programs.Results Seventy-six samples(23.1%)were positive for HRSV.The percentage of cases in patients younger than 1year was 84.21%.Among the six Beijing isolates,four belonged to subgroup A,whose respective F genes shared97.0%-97.4%nucleotide sequence identity and 92.1%-93.0%amino acid sequence identity.The other two isolates belonged to subgroup B.Here,97.3%and 98.2%sequence identity were found at nucleotide and amino acid levels,respectively.Conclusions Phylogenetic analysis of nucleotide sequences revealed that those four isolates within subgroup A were monophyletic and closely related to each other,but those two within subgroup B distributed in two distinct clusters.Subgroup A and B strains co-circulated,indicating that two different transmission chains occurred in Beijing from 2003-2004.
文摘Background Respiratory syncytial virus(RSV)is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years,representing a major global healthcare burden.There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life.A multidisciplinary consensus development group comprising experts in epidemiology,infectious diseases,respiratory medicine,and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.Data sources The evidence searches and reviews were conducted using electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Library,using variations in terms for"respiratory syncytial virus","RSV","lower respiratory tract infection","bronchiolitis","acute","viral pneumonia","neonatal","infant""children",and"pediatric".Results Evidence-based recommendations regarding diagnosis,treatment,and prevention were proposed with a high degree of consensus.Although supportive care remains the cornerstone for the management of RSV infections,new monoclonal antibodies,vaccines,drug therapies,and viral surveillance techniques are being rolled out.Conclusions This consensus,based on international and national scientific evidence,reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections.Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.
基金supported by the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(CAMS)(grant number 2021-RC330-002)the Disease Burden of Respiratory Syncytial Virus and Policy Recommendations Project(grant number 202108180001).
文摘Background Respiratory syncytial virus(RSV)infection in infants is a global health priority.We aimed to investigate the common manifestations of RSV infection by age group and human development index(HDI)level and to assess its association with the development of wheezing and recurrent wheezing illness.Methods We searched the literature published between January 1,2010 and June 2,2022 in seven databases.Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children.Random-and fixed-effect models were used to estimate the effect size and their 95%confidence intervals.Subgroup analysis was conducted by age and HDI levels.This review was registered in PROSPERO(CRD42022379401).Results The meta-analysis included 47 studies.The top five manifestations were cough(92%),nasal congestion(58%),rhinorrhea(53%),shortness of breath(50%),and dyspnea(47%).The clinical symptoms were most severe in infants.In our analysis,compared to very high and high HDI countries,fewer studies in medium HDI countries reported related manifestations,and no study in low HDI countries reported that.The RSV-infected infants were more likely to develop wheezing than the non-infected infants[odds ratio(OR),3.12;95%CI,2.59–3.76]and had a higher risk of developing wheezing illnesses after recovery(OR,2.60;95%CI,2.51–2.70).Conclusions Cough and shortness of breath are common manifestations of RSV infection.More attention should be given to infants and areas with low HDI levels.The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.
基金funding support from the School of Pharmacy,University of Pittsburgh(SS),Brenneman Fund,University of Pittsburgh(KME)Graduate Student Research Scholarship from the School of Pharmacy,University of Pittsburgh(AP)special BD LSRFORTESSATM funded by NIH 1S10OD011925-01(PI:Borghesi).
文摘Respiratory syncytial virus(RSV)is the most common cause of viral bronchiolitis among children worldwide,yet there is no vaccine for RSV disease.This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles(CNP)to modulate reactive oxygen(ROS)and nitrogen(RNS)species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo.Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods,respectively.Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential.In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages.Specifically,cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels.Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFαand IL-12p70,while simultaneously decreasing M2 CD206 expression.Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice.Notably,cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation,avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils,which are associated with RSV-mediated inflammation.In conclusion,we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection.
基金National Key Research and Development Program of China(2018YFC1603803)National Natural Science Foun-dation of China(31970548)+2 种基金Knowledge Innovation Program of Wuhan-Basi Research(2022020801010519)Health Commission of Hubei Province(WJ 2021M262)Natural Science Fund of Hubei Province(2021CFA012).
文摘Human respiratory syncytial virus(RSV)is a severe threat to children and a main cause of acute lower respiratory tract infections.Nevertheless,the intra-host evolution and inter-regional diffusion of RSV are little known.In this study,we performed a systematic surveillance in hospitalized children in Hubei during 2020–2021,in which 106 RSV-positive samples were detected both clinically and by metagenomic next generation sequencing(mNGS).RSV-A and RSV-B groups co-circulated during surveillance with RSV-B being predominant.About 46 high-quality genomes were used for further analyses.A total of 163 intra-host nucleotide variation(iSNV)sites distributed in 34 samples were detected,and glycoprotein(G)gene was the most enriched gene for iSNVs,with non-synonymous substitutions more than synonymous substitutions.Evolutionary dynamic analysis showed that the evolutionary rates of G and NS2 genes were higher,and the population size of RSV groups changed over time.We also found evidences of inter-regional diffusion from Europe and Oceania to Hubei for RSV-A and RSV-B,respectively.This study highlighted the intra-host and inter-host evolution of RSV,and provided some evi-dences for understanding the evolution of RSV.
基金supported by a grant from the Priority Academic Program Development of Jiangsu Higher Education Institution(JX10231801).
文摘Background:The influence of Mycoplasma pneumoniae(MP)infection on bronchiolitis remains unclear.Additionally,reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been inconclusive.Methods:Children with respiratory syncytial virus(RSV)-induced bronchiolitis were divided into two groups:RSV+MP group and RSV group.Each group was randomly divided into two subgroups:one received routine and placebo treatment,while the other received routine and montelukast treatment for 9 months.The cumulative numbers of wheezing episodes and recurrent respiratory tract infections were recorded.Blood parameters were determined.Results:Patients in the RSV+MP group exhibited an older average age,fever,more frequent flaky and patchy shadows in chest X-rays,more frequent extrapulmonary manifestations,and longer hospital stays compared with patients in the RSV group.Additionally,higher baseline blood eosinophil counts,eosinophil cationic protein(ECP),total immunoglobulin E(IgE),interleukin(IL)-4,IL-5,IL-4/interferon-γratios,leukotriene(LT)B4,and LTC4,and lower baseline lipoxin A4(LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the RSV group.Montelukast treatment decreased the cumulative numbers of recurrent wheezing episodes and recurrent respiratory tract infections at 9 and 12 months.This efficacy may be related to the montelukast-induced reductions in peripheral eosinophil counts,ECP and total IgE,as well as the montelukast-dependent recovery in T helper(Th)1/Th2 balance and LXA4/LTB4 ratios in children with bronchiolitis.Conclusions:RSV bronchiolitis with MP infection was associated with clinical and laboratory features that differed from those of RSV bronchiolitis without MP infection.Add-on therapy with montelukast for 9 months was benefi cial for children with bronchiolitis at 9 and 12 months after the initiation of treatment.
基金This work was supported by grants from the Natural Science Foundation of China(81771777,32070922).
文摘Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice.The constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain(A2cpts)or further combined with SH gene deletion(A2cptsΔSH),HDV ribozyme(δ),and a T7 terminator.These vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2-1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero cells.The rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2cp,rRSV-Long/A2cpts,and rRSV-Long/A2cptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or deletion.Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in vivo.Furthermore,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory disease.We showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of rRSV.By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.
基金financially supported by the National Natural Science Foundation of China(21605126)the Fund of Chongqing Research Program of Basic Research and Frontier Technology(cstc2017jcyjAX0091)the Fundamental Research Funds for the Central Universities(SWU118015)
文摘Accurate diagnosis of early infections caused by the viral pathogen is a major challenge because patients usually have nonspecific signs.The development of sensitive,reliable,robust,and rapid laboratory tools is still in high demand.Herein,we developed an extremely sensitive and affordable plasmonic immunoassay for respiratory syncytial virus(RSV)detection with the naked eye based on gold nanoparticles(AuNPs)/graphene hybrids combined with metal enhancement solution.The limit of detection was found to be 1.7 fg/mL,which was 100 times higher than that of the AuNPs-based method.The ultrahigh sensitivity could be attributed to the large number of well-dispersed AuNPs deposited on the graphene surface,which had an extremely high relative surface area.Further signal amplification was achieved by catalytic enlargement of AuNPs with HAuCl_(4)-NH_(2)OH redox reaction.Moreover,the plasmonic immunoassay was successfully used to detect RSV in artificial serum samples,showing great potential in practical applications.
基金This work was supported by the National Science and Technology Major Projects(Grant Number 2017ZX10104001-005-010,2017ZX10103004-004)the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant Number 2019-I2M-5-026)。
文摘Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.
文摘Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature search including EMBASE,MEDLINE,and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant,prematurity,and BPD between 1980 and 2014.Results:Recurrent respiratory symptoms remain common at preschool age,school age and even into young adulthood.Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the fi rst years of life.Infl uenza virus infection plays a minor role compared to respiratory syncytial virus(RSV)associated respiratory tract infection during infancy and early childhood.Nevertheless,particular morbidity to both viruses is high.Conclusions:The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the fi rst two years of life.Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months,and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.
文摘Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.
基金This work was supported by the National key R&D program of China(2017YFA0505801)the National Natural Science Foundation of China(11831015)。
文摘Respiratory syncytial virus(RSV) is the major cause of lower respiratory tract infections in children. Inactivated RSV vaccine was developed in the late 1960’s, but the vaccine-enhanced disease(VED) occurred to vaccinated infants upon subsequent natural RSV infection. The excessive inflammatory immunopathology in the lungs might be involved in the VED, but the underlying mechanisms remain not fully understood. In this study, we utilized UV-inactivated RSV in the prime/boost approach followed by RSV challenge in BALB/c mice to mimic RSV VED. The dynamic virus load,cytokines, histology and transcriptome profiles in lung tissues of mice were investigated from day 1 to day 6 post-infection.Compared to PBS-treated mice, UV-RSV vaccination leads to a Th2 type inflammatory response characterized by enhanced histopathology, reduced Treg cells and increased IL4^(+)CD4 T cells in the lung. Enhanced production of several Th2 type cytokines(IL-4, IL-5, IL-10) and TGF-b, reduction of IL-6 and IL-17 were observed in UV-RSV vaccinated mice. A total of 5582 differentially expressed(DE) genes between PBS-treated or vaccinated mice and na?ve mice were identified by RNA-Seq. Eleven conserved high-influential modules(HMs) were recognized, majorly grouped into regulatory networks related to cell cycle and cell metabolism, signal transduction, immune and inflammatory responses. At an early time post-infection, the vaccinated mice showed obvious decreased expression patterns of DE genes in 11 HMs compared to PBS-treated mice. The extracellular matrix(HM5) and immune responses(HM8) revealed tremendous differences in expression and regulation characteristics of transcripts between PBS-treated and vaccinated mice at both early and late time points. The highly connected genes in HM5 and HM8 networks were further validated by RT-qPCR.These findings reveal the relationship between RSV VED and immune responses, which could benefit the development of novel RSV vaccines.
基金Supported by Medical Guide Project of Shanghai Municipal Science and Technology Commission(No.134119a4200)Shanghai municipal commission of health and family planning(No.20134249).
文摘Background:To investigate the clinical characteristics and analyze risk factors for severe respiratory syncytial virus(RSV)infection in hospitalized infants with acute lower respiratory tract infections(ALRIs).Methods:A retrospective review of the medical records of infants with RSV-associated ALRIs between March 1st,2011 and February 29th,2012 was conducted.Subjects were followed up over the phone or by outpatient visit six and twelve months after discharge.Results:Among 913 RSV-associated ALRIs infants,288(31.5%)had severe infections,which accounted for 4.2%of hospitalized children.The hospital RSV mortality rate was 1.0%.The proportions of cases with tachypnea,apnea,cyanosis,and fine rales were significantly higher in the severe ALRIs group(all P<0.001).Multivariate logistic regression showed that low-birth-weight[1.698(1.028-2.805)],age less than 3 months old[3.385(2.174-5.271)],congenital heart disease[1.667(1.149-2.418)],bronchopulmonary dysplasia[8.505(1.731-41.780)],and airway abnormalities[2.246(1.008-5.005)]were independent risk factors for severe ALRIs.The incidence of bronchitis,pneumonia and readmission in the severe group was significantly higher than that of the non-severe group during the one-year follow-up(all P<0.001).Conclusions:Younger age,low birth weight and underlying disease are associated with severe RSVassociated ALRIs.Furthermore,severe RSV infections may be associated with a higher frequency of subsequent bronchitis,pneumonia and re-hospitalization in the following year.
文摘Respiratory Syncytial Viral Infection is one of the most common viral infections in the respiratory airways and is more common in infants, younger children and some adults. Although ribavirin has been used in the management of RSV infection, many effective drugs are still under development. Also, structured based drug design using computational tools has shifted the paradigm of drug design and discovery. The fusion core of the Respiratory Syncytial Viral (RSV) structure is crucial for its fusion, entry and replication in the host cell. Herein, we investigated the interruption of the formation and/or the stability of the fusion core. 15 ligands were screened and 4 (Glimepiride, Glipizide, Canagloflozin, Glibenclamide) of them are potential drug candidate for experimental validation, preclinical trials, clinical trials and route of administration optimization. To the best of our knowledge, this is the first time of reporting lead molecules against RSV from oral hypoglycemic agents. It also suggests the ligands for consideration as prophylactics in infants and adults via the inhalation route.
基金supported by the National Natural Science Foundation of China(NSFC)(81991494 and 82122031)the National Key R&D Program of China(2020YFA0907100)+3 种基金the Chinese Academy of Sciences(YSBR-010)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-026)Beijing Natural Science Foundation(L222076)L.D.is supported by the Youth Innovation Promotion Association CAS,China(2018113).
文摘Respiratory syncytial virus(RSV)is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly.Passive immunoprophylaxis with monoclonal antibody(mAb)has been approved to prevent morbidity and mortality from RSV infection in infants.Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion(F)glycoprotein as bait.One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay,and protected mice from RSV infection in vivo.An RV11 escape mutant was identified,which contains an S443P mutation in F protein.Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites IV and V of the F glycoprotein.RV11 showed a strong synergistic effect when combined with two RSV antivirals,an F-targeting small molecular inhibitor ziresovir and a siteØneutralizing mAb D25(the parental mAb for nirsevimab).The study extended our knowledge to the neutralizing and protective epitopes of RSV,and the mAb RV11 deserves further development for clinical translation.
