As a response factor of interferon,tripartite motif(TRIM)22 was reported to exert antiviral activity against viruses.In this study,THP-1 macrophages were infected with human cytomegalovirus(HCMV)to establish the HCMV ...As a response factor of interferon,tripartite motif(TRIM)22 was reported to exert antiviral activity against viruses.In this study,THP-1 macrophages were infected with human cytomegalovirus(HCMV)to establish the HCMV lytic infection model.The mRNA levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)and interferonbeta(IFN-β)were significantly up-regulated in THP-1 macrophages at different infection time and titers.Moreover,for the first time,upregulation of TRIM22 expression was found during HCMV infection at both mRNA and protein levels in THP-1 macrophages.Furthermore,IFN-β could induce TRIM22 expression in THP-1 macrophages or HCMV infected THP-1 macrophages.Depletion of TRIM22 increased replication activity of HCMV with increasing of HCMV titers and HCMV proteins.In conclusion,it is the first report that HCMV can induce TRIM22 activation through IFN-β signaling and TRIM22 can suppress replication of HCMV in THP-1 macrophages.展开更多
Rasmussen's encephalitis(RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses, including human cytomegalovirus(HCMV), has been speculated to be a potential trigger fo...Rasmussen's encephalitis(RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses, including human cytomegalovirus(HCMV), has been speculated to be a potential trigger for RE. However, no viral antigens have been detected in the brains of patients with RE; thus, a possible clinical linkage between viral infections and RE has not been firmly established. In this study, we evaluated the expression of HCMV pp65 antigen in brain sections from 26 patients with RE and 20 non-RE patients by immunohistochemistry and in situ hybridization, and assessed the associations between HCMV infection and clinical parameters.Elevated expression of HCMV pp65 protein and DNA was observed in 88.5%(23/26) and 69.2%(18/26) of RE cases, respectively. In the non-RE group, HCMV pp65 antigen was detected only in two cases(10%), both of which were negative for DNA staining. Additionally, the intensity of HCMV pp65 staining was correlated with a shorter duration of the prodromal stage, younger age of seizure onset, and more severe unilateral cortical atrophy. Elevated expression of HCMV pp65 was observed in RE brain tissue and was correlated with the clinical features of RE disease. In summary, our results suggested that HCMV infection may be involved in the occurrence and progression of RE disease. Thus, further studies are needed to determine whether early treatment with anti-HCMV antibodies could modulate the course of RE.展开更多
Human cytomegalovirus(HCMV)is a double-strand DNA virus widely infected in human.Circular RNAs(circ RNAs)are non-coding RNAs with most functions of which keep unknown,and the effects of HCMV productive infection on ho...Human cytomegalovirus(HCMV)is a double-strand DNA virus widely infected in human.Circular RNAs(circ RNAs)are non-coding RNAs with most functions of which keep unknown,and the effects of HCMV productive infection on host circ RNA transcriptions remain unclear.In this study,we profiled 283 host circ RNAs that significantly altered by HCMV productive infection in human embryonic lung fibroblasts(HELF)by RNA deep sequencing and bioinformatics analysis.Among these,circ SP100,circ MAP3 K1,circ PLEKHM1,and circ TRIO were validated for their transcriptions and sequences.Furthermore,characteristics of circ SP100 were investigated by RT-q PCR and northern blot.It was implied that circ SP100 was produced from the sense strand of the SP100 gene containing six exons.Kinetics of circ SP100 and SP100 m RNA were significantly different after infection:circ SP100 levels increased gradually along with infection,whereas SP100 m RNA levels increased in the beginning and dropped at 24 h post-infection(hpi).Meanwhile,a total number of 257 proteins,including 10 HCMV encoding proteins,were identified potentially binding to cytoplasmic circ SP100 by RNA antisense purification(RAP)and mass spectrometry.Enrichment analysis showed these proteins were mainly involved in the spliceosome,protein processing,ribosome,and phagosome pathways,suggesting multiple functions of circ SP100 during HCMV infection.展开更多
Viruses commonly create favorable cellular conditions for their survival through multiple mechanisms. Micro RNAs(mi RNAs), which function as post-transcriptional regulators, are utilized by human cytomegalovirus(HCMV)...Viruses commonly create favorable cellular conditions for their survival through multiple mechanisms. Micro RNAs(mi RNAs), which function as post-transcriptional regulators, are utilized by human cytomegalovirus(HCMV) in its infection and pathogenesis. In the present study, the DNA replication inhibitor Geminin(GMNN) was identified to be a direct target of hcmv-mi R-US5-1. Overexpression of hcmv-mi R-US5-1 could block the accumulation of GMNN during HCMV infection, and the decrease of GMNN expression caused by hcmv-mi R-US5-1 or GMNN specific si RNA reduced HCMV DNA copies in U373 cells. Meanwhile, ectopic expression of hcmv-mi R-US5-1 and consequent lower expression of GMNN influenced host cell cycle and proliferation. These results imply that hcmv-mi R-US5-1 may affect viral replication and host cellular environment by regulating expression kinetics of GMNN during HCMV infection.展开更多
Current drugs for treating human cytomegalovirus(HCMV)infections are limited by resistance and treatment-associated toxicities.In developing mechanistically novel HCMV antivirals,we discovered an N-benzyl hydroxypyrid...Current drugs for treating human cytomegalovirus(HCMV)infections are limited by resistance and treatment-associated toxicities.In developing mechanistically novel HCMV antivirals,we discovered an N-benzyl hydroxypyridone carboxamide antiviral hit(8a)inhibiting HCMV in submicromolar range.We describe herein the structure–activity relationship(SAR)for 8a,and the characterization of potent analogs for cytotoxicity/cytostatic property,the preliminary mechanism of action,and the absorption,distribution,metabolism and excretion(ADME)properties.The SAR revealed a few pharmacophore features conferring optimal antiviral profile,including the 5-OH,the N-1 benzyl,at least one–CH_(2)−in the linker,and a di-halogen substituted phenyl ring in the amide moiety.In the end,we identified numerous analogs with sub-micromolar antiviral potency and good selectivity index.The preliminary mechanism of action characterization used a pUL89-C biochemical endonuclease assay,a virus entry assay,a time-of-addition assay,and a compound withdrawal assay.ADME profiling measuring aqueous solubility,plasma and liver microsomal stability,and parallel artificial membrane permeability assay(PAMPA)permeability demonstrated largely favorable drug-like properties.Together,these studies validate the N-benzyl hydroxypyridone carboxamide as a viable chemotype for potent and mechanistically distinct antivirals against HCMV.展开更多
Human cytomegalovirus(HCMV)is a ubiquitous pathogen belongs to betaherpesvirus subfamily.RNA2.7 is a highly conserved long non-coding RNA accounting for more than 20%of total viral transcripts.In our study,functions o...Human cytomegalovirus(HCMV)is a ubiquitous pathogen belongs to betaherpesvirus subfamily.RNA2.7 is a highly conserved long non-coding RNA accounting for more than 20%of total viral transcripts.In our study,functions of HCMV RNA2.7 were investigated by comparison of host cellular transcriptomes between cells infected with HCMV clinical strain and RNA2.7 deleted mutant.It was demonstrated that RNA polymeraseⅡ(PolⅡ)-dependent host gene transcriptions were significantly activated when RNA2.7 was removed during infection.A145 nt-in-length motif within RNA2.7 was identified to inhibit the phosphorylation of PolⅡSerine-2(PolⅡS2)by reducing the interaction between PolⅡand phosphorylated cyclin-dependent kinase 9(pCDK9).Due to the loss of PolⅡS2 phosphorylation,cellular DNA pre-replication complex(pre-RC)factors,including Cdt1 and Cdc6,were significantly decreased,which prevented more cells from entering into S phase and facilitated viral DNA replication.Our results provide new insights of HCMV RNA2.7 functions in regulation of host cellular transcription.展开更多
Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to i...Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to its anticancer activity,SAHA has significant effects on the growth of many viruses. The effect of SAHA on replication of human cytomegalovirus(HCMV) has not, however, been investigated. Here, we showed that the replication of HCMV was significantly suppressed by treatment with SAHA at concentrations that did not show appreciable cytotoxicity. SAHA reduced transcription and protein levels of HCMV immediate early genes, showing that SAHA acts at an early stage in the viral life-cycle. RNAsequencing data mining showed that numerous pathways and molecules were affected by SAHA. Interferon-mediated immunity was one of the most relevant pathways in the RNA-sequencing data, and we confirmed that SAHA inhibits HCMV-induced IFN-mediated immune responses using quantitative Real-time PCR(qRT-PCR). Fatty acid-binding protein 4(FABP4), which plays a role in lipid metabolism, was identified by RNA-sequencing. We found that FABP4 expression was reduced by HCMV infection but increased by treatment with SAHA. We then showed that knockdown of FABP4 partially rescued the effect of SAHA on HCMV replication. Our data suggest that FABP4 contributes to the inhibitory effect of SAHA on HCMV replication.展开更多
Objective To investigate the relationship between human cytomegalovirus(HCMV)infection and peripheral blood CD14+CD16+monocytes in the pathogenesis of coronary heart disease(CHD),and to elucidate the mechanism of path...Objective To investigate the relationship between human cytomegalovirus(HCMV)infection and peripheral blood CD14+CD16+monocytes in the pathogenesis of coronary heart disease(CHD),and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection,inflammation,and CHD,to provide a basis for the prevention,evaluation,and treatment of the disease.Methods In total,192 patients with CHD were divided into three groups:latent CHD,angina pectoris,and myocardial infarction.HCMV-IgM and-IgG antibodies were assessed using ELISA;CD14+CD16+monocytes were counted using a five-type automated hematology analyzer;mononuclear cells were assessed using fluorescence-activated cell sorting;and an automatic biochemical analyzer was used to measure the levels of triglyceride,cholesterol,high-and low-density lipoprotein cholesterols,lipoprotein,hs-CRp and Hcy.Results The positive rates of HCMV-IgM and-IgG were significantly higher in the CHD groups than in the control group.HCMV infection affects lipid metabolism to promote immune and inflammatory responses.Conclusion HCMV infection has a specific correlation with the occurrence and development of CHD.The expression of CD14+CD16+mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection.Thus,HCMV antibody as well as peripheral blood CD14+CD16+mononuclear cells can be used to monitor the occurrence and development of CHD.展开更多
DNA of human cytomegalovirus (HCMV) contains three transforming fragments, which have been mapped in the long unique region of the viral genome(see Fig.1). A minimal region of 558 base pairs(bp) (pCM4127) was localize...DNA of human cytomegalovirus (HCMV) contains three transforming fragments, which have been mapped in the long unique region of the viral genome(see Fig.1). A minimal region of 558 base pairs(bp) (pCM4127) was localized in the XbaI-Hindlll fragment of HCMV strain AD169 (mapunit 0.123—0.140)and designated morphological transforming region Ⅰ (mtrⅠ). MtrⅠwas reported to cause one-step focal transformation of primary展开更多
Human cytomegalovirus(HCMV), a herpesvirus, is an important human pathogen that causes asymptomatic infections in healthy or immunocompetent individuals but can lead to severe and potentially life-threatening complica...Human cytomegalovirus(HCMV), a herpesvirus, is an important human pathogen that causes asymptomatic infections in healthy or immunocompetent individuals but can lead to severe and potentially life-threatening complications in immune-immature individuals such as neonates or immune-compromised patients such as organ-transplant recipients and HIV-positive individuals.Congenital HCMV infection represents a significant public health issue and poses substantial healthcare and economic burden to society. This virus causes the most common viral congenital infection worldwide, and is the leading non-genetic cause of sensorineural hearing loss in children in developed countries. Congenital HCMV infection is believed to fulfill the criteria of the American College of Medical Genetics to be considered as a condition targeted for a newborn screening program. This is because congenital HCMV infection can be identified during a time(within 2 days after birth) at which it would not ordinarily be detected clinically, and there are demonstrated benefits of early detection, timely intervention, and efficacious treatment of the condition. Recent progresses in developing polymerase chain reaction-based approaches to detect HCMV in samples obtained from newborns have generated much excitement in the field. In this review, we highlight the recent progress in diagnostic techniques that could potentially be used for the detection of HCMV infection in neonates and its direct implications in public health settings for diagnosing congenital HCMV infection.展开更多
Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell recon...Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell reconstitution may protect against the development of human CMV (HCMV) infection post-HSCT. Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells. Nevertheless, whether expanded NK cells have stronger anti-HCMV function is unknown. Herein, we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells. Expanded NK cells showed higher expression of activating receptors, chemokine receptors and adhesion molecules;stronger cytotoxicity against HCMV-infected fibroblasts;and better inhibition of HCMV propagation in vitro than primary NK cells. In HCMV-infected humanized mice, expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion. A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection (HR = 0.54, 95% CI = 0.32–0.93, p = 0.042) and refractory HCMV infection (HR = 0.34, 95% CI = 0.18–0.65, p = 0.009) than controls and better NK cell reconstitution on day 30 post NK cell infusion. In conclusion, expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.展开更多
基金funded by the National Nature Science Foundation of China(81701535 and 81671495)the Medical Scientific Projects from Health Department of Zhejiang Province(2015KYA119)the National Nature Science Foundation of Zhejiang(LQ18H040001)and Ai You Foundation.
文摘As a response factor of interferon,tripartite motif(TRIM)22 was reported to exert antiviral activity against viruses.In this study,THP-1 macrophages were infected with human cytomegalovirus(HCMV)to establish the HCMV lytic infection model.The mRNA levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)and interferonbeta(IFN-β)were significantly up-regulated in THP-1 macrophages at different infection time and titers.Moreover,for the first time,upregulation of TRIM22 expression was found during HCMV infection at both mRNA and protein levels in THP-1 macrophages.Furthermore,IFN-β could induce TRIM22 expression in THP-1 macrophages or HCMV infected THP-1 macrophages.Depletion of TRIM22 increased replication activity of HCMV with increasing of HCMV titers and HCMV proteins.In conclusion,it is the first report that HCMV can induce TRIM22 activation through IFN-β signaling and TRIM22 can suppress replication of HCMV in THP-1 macrophages.
基金supported by the following funds: the National Natural Science Foundation of China (81571275)the Beijing Municipal Natural Science Foundation (7144217)+5 种基金the Capital Applied Clinic Research Programs of Science and Technology (Z131107002213171)the Beijing Rising-star Plan of Science and Technology (Z141107001814042)the Open Research Fund of the Beijing Key Laboratory of Epilepsy Research (No. 2014DXBL02)Capital Medical University (15JL08)Scientific Research Common Program of Beijing Municipal Commission of Education (KM201610025001)Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (2014 1685)
文摘Rasmussen's encephalitis(RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses, including human cytomegalovirus(HCMV), has been speculated to be a potential trigger for RE. However, no viral antigens have been detected in the brains of patients with RE; thus, a possible clinical linkage between viral infections and RE has not been firmly established. In this study, we evaluated the expression of HCMV pp65 antigen in brain sections from 26 patients with RE and 20 non-RE patients by immunohistochemistry and in situ hybridization, and assessed the associations between HCMV infection and clinical parameters.Elevated expression of HCMV pp65 protein and DNA was observed in 88.5%(23/26) and 69.2%(18/26) of RE cases, respectively. In the non-RE group, HCMV pp65 antigen was detected only in two cases(10%), both of which were negative for DNA staining. Additionally, the intensity of HCMV pp65 staining was correlated with a shorter duration of the prodromal stage, younger age of seizure onset, and more severe unilateral cortical atrophy. Elevated expression of HCMV pp65 was observed in RE brain tissue and was correlated with the clinical features of RE disease. In summary, our results suggested that HCMV infection may be involved in the occurrence and progression of RE disease. Thus, further studies are needed to determine whether early treatment with anti-HCMV antibodies could modulate the course of RE.
基金supported by the National Natural Science Foundation of China (81672028 and 81371788)。
文摘Human cytomegalovirus(HCMV)is a double-strand DNA virus widely infected in human.Circular RNAs(circ RNAs)are non-coding RNAs with most functions of which keep unknown,and the effects of HCMV productive infection on host circ RNA transcriptions remain unclear.In this study,we profiled 283 host circ RNAs that significantly altered by HCMV productive infection in human embryonic lung fibroblasts(HELF)by RNA deep sequencing and bioinformatics analysis.Among these,circ SP100,circ MAP3 K1,circ PLEKHM1,and circ TRIO were validated for their transcriptions and sequences.Furthermore,characteristics of circ SP100 were investigated by RT-q PCR and northern blot.It was implied that circ SP100 was produced from the sense strand of the SP100 gene containing six exons.Kinetics of circ SP100 and SP100 m RNA were significantly different after infection:circ SP100 levels increased gradually along with infection,whereas SP100 m RNA levels increased in the beginning and dropped at 24 h post-infection(hpi).Meanwhile,a total number of 257 proteins,including 10 HCMV encoding proteins,were identified potentially binding to cytoplasmic circ SP100 by RNA antisense purification(RAP)and mass spectrometry.Enrichment analysis showed these proteins were mainly involved in the spliceosome,protein processing,ribosome,and phagosome pathways,suggesting multiple functions of circ SP100 during HCMV infection.
基金supported by the National Natural Science Foundation of China (81371788 and 81171580)the Specialized Research Fund for the Doctoral Program of Higher Education (20112104110012)the Outstanding Scientific Fund of Shengjing Hospital
文摘Viruses commonly create favorable cellular conditions for their survival through multiple mechanisms. Micro RNAs(mi RNAs), which function as post-transcriptional regulators, are utilized by human cytomegalovirus(HCMV) in its infection and pathogenesis. In the present study, the DNA replication inhibitor Geminin(GMNN) was identified to be a direct target of hcmv-mi R-US5-1. Overexpression of hcmv-mi R-US5-1 could block the accumulation of GMNN during HCMV infection, and the decrease of GMNN expression caused by hcmv-mi R-US5-1 or GMNN specific si RNA reduced HCMV DNA copies in U373 cells. Meanwhile, ectopic expression of hcmv-mi R-US5-1 and consequent lower expression of GMNN influenced host cell cycle and proliferation. These results imply that hcmv-mi R-US5-1 may affect viral replication and host cellular environment by regulating expression kinetics of GMNN during HCMV infection.
基金This research was supported by the National Institute of Allergy and Infectious Diseases,the National Institutes of Health,United States grant number R01AI136982(to Robert J.Geraghty and Zhengqiang Wang,USA).
文摘Current drugs for treating human cytomegalovirus(HCMV)infections are limited by resistance and treatment-associated toxicities.In developing mechanistically novel HCMV antivirals,we discovered an N-benzyl hydroxypyridone carboxamide antiviral hit(8a)inhibiting HCMV in submicromolar range.We describe herein the structure–activity relationship(SAR)for 8a,and the characterization of potent analogs for cytotoxicity/cytostatic property,the preliminary mechanism of action,and the absorption,distribution,metabolism and excretion(ADME)properties.The SAR revealed a few pharmacophore features conferring optimal antiviral profile,including the 5-OH,the N-1 benzyl,at least one–CH_(2)−in the linker,and a di-halogen substituted phenyl ring in the amide moiety.In the end,we identified numerous analogs with sub-micromolar antiviral potency and good selectivity index.The preliminary mechanism of action characterization used a pUL89-C biochemical endonuclease assay,a virus entry assay,a time-of-addition assay,and a compound withdrawal assay.ADME profiling measuring aqueous solubility,plasma and liver microsomal stability,and parallel artificial membrane permeability assay(PAMPA)permeability demonstrated largely favorable drug-like properties.Together,these studies validate the N-benzyl hydroxypyridone carboxamide as a viable chemotype for potent and mechanistically distinct antivirals against HCMV.
基金supported by the National Natural Science Foundation of China(82071664)。
文摘Human cytomegalovirus(HCMV)is a ubiquitous pathogen belongs to betaherpesvirus subfamily.RNA2.7 is a highly conserved long non-coding RNA accounting for more than 20%of total viral transcripts.In our study,functions of HCMV RNA2.7 were investigated by comparison of host cellular transcriptomes between cells infected with HCMV clinical strain and RNA2.7 deleted mutant.It was demonstrated that RNA polymeraseⅡ(PolⅡ)-dependent host gene transcriptions were significantly activated when RNA2.7 was removed during infection.A145 nt-in-length motif within RNA2.7 was identified to inhibit the phosphorylation of PolⅡSerine-2(PolⅡS2)by reducing the interaction between PolⅡand phosphorylated cyclin-dependent kinase 9(pCDK9).Due to the loss of PolⅡS2 phosphorylation,cellular DNA pre-replication complex(pre-RC)factors,including Cdt1 and Cdc6,were significantly decreased,which prevented more cells from entering into S phase and facilitated viral DNA replication.Our results provide new insights of HCMV RNA2.7 functions in regulation of host cellular transcription.
基金This research was supported by National Key R&D Program of China Grant(2016YFA0502101)National Natural Science Foundation of China(grants 81371826 and 81572002 to Z.Q.,grants 31300148 and 31570169)。
文摘Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to its anticancer activity,SAHA has significant effects on the growth of many viruses. The effect of SAHA on replication of human cytomegalovirus(HCMV) has not, however, been investigated. Here, we showed that the replication of HCMV was significantly suppressed by treatment with SAHA at concentrations that did not show appreciable cytotoxicity. SAHA reduced transcription and protein levels of HCMV immediate early genes, showing that SAHA acts at an early stage in the viral life-cycle. RNAsequencing data mining showed that numerous pathways and molecules were affected by SAHA. Interferon-mediated immunity was one of the most relevant pathways in the RNA-sequencing data, and we confirmed that SAHA inhibits HCMV-induced IFN-mediated immune responses using quantitative Real-time PCR(qRT-PCR). Fatty acid-binding protein 4(FABP4), which plays a role in lipid metabolism, was identified by RNA-sequencing. We found that FABP4 expression was reduced by HCMV infection but increased by treatment with SAHA. We then showed that knockdown of FABP4 partially rescued the effect of SAHA on HCMV replication. Our data suggest that FABP4 contributes to the inhibitory effect of SAHA on HCMV replication.
基金Funded by the National Natural Science Foundation of China[81471048]the Natural Science Foundation of Shandong Province[ZR2019MC059]Shandong Province Government-Sponsored Overseas Study Project.&These authors contributed equally to this work.
文摘Objective To investigate the relationship between human cytomegalovirus(HCMV)infection and peripheral blood CD14+CD16+monocytes in the pathogenesis of coronary heart disease(CHD),and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection,inflammation,and CHD,to provide a basis for the prevention,evaluation,and treatment of the disease.Methods In total,192 patients with CHD were divided into three groups:latent CHD,angina pectoris,and myocardial infarction.HCMV-IgM and-IgG antibodies were assessed using ELISA;CD14+CD16+monocytes were counted using a five-type automated hematology analyzer;mononuclear cells were assessed using fluorescence-activated cell sorting;and an automatic biochemical analyzer was used to measure the levels of triglyceride,cholesterol,high-and low-density lipoprotein cholesterols,lipoprotein,hs-CRp and Hcy.Results The positive rates of HCMV-IgM and-IgG were significantly higher in the CHD groups than in the control group.HCMV infection affects lipid metabolism to promote immune and inflammatory responses.Conclusion HCMV infection has a specific correlation with the occurrence and development of CHD.The expression of CD14+CD16+mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection.Thus,HCMV antibody as well as peripheral blood CD14+CD16+mononuclear cells can be used to monitor the occurrence and development of CHD.
文摘DNA of human cytomegalovirus (HCMV) contains three transforming fragments, which have been mapped in the long unique region of the viral genome(see Fig.1). A minimal region of 558 base pairs(bp) (pCM4127) was localized in the XbaI-Hindlll fragment of HCMV strain AD169 (mapunit 0.123—0.140)and designated morphological transforming region Ⅰ (mtrⅠ). MtrⅠwas reported to cause one-step focal transformation of primary
基金supported by grants from Guangdong Innovative and Entrepreneurial Research Team Program (No. 2014 ZT05S136)the National Mega Project on Major Infectious Disease Prevention (2012ZX10002006-003 and 2012 ZX10004-207)NIH (RO1-AI041927, RO1-AI091536, RO1-DE023935, and RO1-DE025462)
文摘Human cytomegalovirus(HCMV), a herpesvirus, is an important human pathogen that causes asymptomatic infections in healthy or immunocompetent individuals but can lead to severe and potentially life-threatening complications in immune-immature individuals such as neonates or immune-compromised patients such as organ-transplant recipients and HIV-positive individuals.Congenital HCMV infection represents a significant public health issue and poses substantial healthcare and economic burden to society. This virus causes the most common viral congenital infection worldwide, and is the leading non-genetic cause of sensorineural hearing loss in children in developed countries. Congenital HCMV infection is believed to fulfill the criteria of the American College of Medical Genetics to be considered as a condition targeted for a newborn screening program. This is because congenital HCMV infection can be identified during a time(within 2 days after birth) at which it would not ordinarily be detected clinically, and there are demonstrated benefits of early detection, timely intervention, and efficacious treatment of the condition. Recent progresses in developing polymerase chain reaction-based approaches to detect HCMV in samples obtained from newborns have generated much excitement in the field. In this review, we highlight the recent progress in diagnostic techniques that could potentially be used for the detection of HCMV infection in neonates and its direct implications in public health settings for diagnosing congenital HCMV infection.
基金supported by the National Key Research and Development Program of China (grant 2022YFA1103300)Major of the National Natural Science Foundation of China (No.82293630)+2 种基金Key Program of the National Natural Science Foundation of China (No. 81930004)National Natural Science Foundation of China (grants 81870140, 82070184, 82270228 and 81370666)It was further supported through the Peking University People’s Hospital Research and Development Funds (grant RDX2019-14, RDL2021-01).
文摘Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell reconstitution may protect against the development of human CMV (HCMV) infection post-HSCT. Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells. Nevertheless, whether expanded NK cells have stronger anti-HCMV function is unknown. Herein, we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells. Expanded NK cells showed higher expression of activating receptors, chemokine receptors and adhesion molecules;stronger cytotoxicity against HCMV-infected fibroblasts;and better inhibition of HCMV propagation in vitro than primary NK cells. In HCMV-infected humanized mice, expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion. A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection (HR = 0.54, 95% CI = 0.32–0.93, p = 0.042) and refractory HCMV infection (HR = 0.34, 95% CI = 0.18–0.65, p = 0.009) than controls and better NK cell reconstitution on day 30 post NK cell infusion. In conclusion, expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.
