Co-infections of the central nervous system (CNS) caused by bacterial and viral pathogens are considered to be rare. Herpes simplex virus type-1 (HSV-1) reactivation following Streptococcus pneumoniae infection is wel...Co-infections of the central nervous system (CNS) caused by bacterial and viral pathogens are considered to be rare. Herpes simplex virus type-1 (HSV-1) reactivation following Streptococcus pneumoniae infection is well described but most cases are related to oral or cutaneous lesions or in respiratory samples. HSV-1 CNS reactivation after Streptococcus pneumoniae meningitis is a very rare event and may have significant morbidity and mortality. In this case report, we describe a 71-year-old female patient that presented with a history of abdominal pain and confusion/disorientation that had tonic-clonic seizures while in the Emergency Department. The diagnostic work-up confirmed CNS co-infection caused by Streptococcus pneumoniae and HSV-1. Of note, beyond age, the patient had no known risk factors for both entities and recovered fully after antibiotic and antiviral therapy. This case underlines that clinicians must be aware of CNS co-infection despite being a rare diagnosis. This should be suspected particularly in patients who present an unusual clinical course of CNS infection.展开更多
Background:Herpes simplex virus type 1(HSV-1)is a ubiquitous infectious pathogen that widely affects human health.To decipher the complicated human-HSV-1 interactions,a comprehensive protein-protein interaction(PPI)ne...Background:Herpes simplex virus type 1(HSV-1)is a ubiquitous infectious pathogen that widely affects human health.To decipher the complicated human-HSV-1 interactions,a comprehensive protein-protein interaction(PPI)network between human and HSV-1 is highly demanded.Methods:To complement the experimental identification of human-HSV-1 PPIs,an integrative strategy to predict proteome-wide PPIs between human and HSV-1 was developed.For each human-HSV-1 protein pair,four popular PPI inference methods,including interolog mapping,the domain-domain interaction-based method,the domain-motif interaction-based method,and the machine learning-based method,were optimally implemented to generate four interaction probability scores,which were further integrated into a final probability score.Results:As a result,a comprehensive high-confidence PPI network between human and HSV-1 was established,covering 10,432 interactions between 4,546 human proteins and 72 HSV-1 proteins.Functional and network analyses of the HSV-1 targeting proteins in the context of human interactome can recapitulate the known knowledge regarding the HSV-1 replication cycle,supporting the overall reliability of the predicted PPI network.Considering that HSV-1 infections are implicated in encephalitis and neurodegenerative diseases,we focused on exploring the biological significance of the brain-specific human-HSV-1 PPIs.In particular,the predicted interactions between HSV-1 proteins and Alzheimer's-disease-related proteins were intensively investigated.Conclusion:The current work can provide testable hypotheses to assist in the mechanistic understanding of the human-HSV-1 relationship and the anti-HSV-1 pharmaceutical target discovery.To make the predicted PPI network and the datasets freely accessible to the scientific community,a user-friendly database browser was released at http://www.zzdlab.com/HintHSV/index.php.展开更多
BACKGROUND Herpes simplex virus(HSV)is a highly infectious pathogen that is easily transmitted via the bodily fluids of an infected individual.This virus usually affects individuals older than six months of age,and ra...BACKGROUND Herpes simplex virus(HSV)is a highly infectious pathogen that is easily transmitted via the bodily fluids of an infected individual.This virus usually affects individuals older than six months of age,and rarely causes lesions or symptoms in younger patients.CASE SUMMARY We present the case of a five-month-old healthy girl who presented with painful herpetic gingivostomatitis and perioral vesicles.We discuss the pathophysiology of primary HSV infection and the effect of maternal antibodies on the infant’s immune system.In addition,we explain the diagnosis,management,and prognosis of HSV infection in young infants.CONCLUSION This case highlights the importance of early diagnosis and management of HSV infections to decrease the risk of developing severe complications and death.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
Herpes simplex virus type 1(HSV-1)causes lifelong infections worldwide,and currently there is no efficient cure or vaccine.HSV-1-derived tools,such as neuronal circuit tracers and oncolytic viruses,have been used exte...Herpes simplex virus type 1(HSV-1)causes lifelong infections worldwide,and currently there is no efficient cure or vaccine.HSV-1-derived tools,such as neuronal circuit tracers and oncolytic viruses,have been used exten-sively;however,further genetic engineering of HSV-1 is hindered by its complex genome structure.In the present study,we designed and constructed a synthetic platform for HSV-1 based on H129-G4.The complete genome was constructed from 10 fragments through 3 rounds of synthesis using transformation-associated recombination(TAR)in yeast,and was named H129-Syn-G2.The H129-Syn-G2 genome contained two copies of the gfp gene and was transfected into cells to rescue the virus.According to growth curve assay and electron microscopy results,the synthetic viruses exhibited more optimized growth properties and similar morphogenesis compared to the parental virus.This synthetic platform will facilitate further manipulation of the HSV-1 genome for the devel-opment of neuronal circuit tracers,oncolytic viruses,and vaccines.展开更多
Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate i...Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate in response to stress or sunlight.Previous studies have demonstrated that viral immediate-early protein ICP0 plays a key role in regulating the balance between lytic and latent infection.Recently,It has been deter-mined that promyelocytic leukemia(PML)nuclear bod-ies(NBs),small nuclear sub-structures,contribute to the repression of HSV-1 infection in the absence of functional ICP0.In this review,we discuss the funda-mentals of the interaction between ICP0 and PML NBs,suggesting a potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1.展开更多
Cytomegalovirus(CMV)is distinct among members of the Herpesviridae family for having the largest dsDNA genome(230 kb).Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid,but mole...Cytomegalovirus(CMV)is distinct among members of the Herpesviridae family for having the largest dsDNA genome(230 kb).Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid,but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described.Here,we report a cryo electron microscopy(cryoEM)structure of the murine cytomegalovirus(MCMV)capsid at a 9.1Åresolution and describe the molecular interactions among the~3000 protein molecules in the MCMV capsid at the secondary structure level.Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling.The major capsid protein(MCP)upper domain(MCPud)containsα-helices andβ-sheets conserved with those in MCPud of herpes simplex virus type 1(HSV-1),with the largest differences identifi ed as a“saddle loop”region,located at the tip of MCPud and involved in interaction with the smallest capsid protein(SCP).Interactions among the bacteriophage HK97-like fl oor domain of MCP,the middle domain of MCP,the hook and clamp domains of the triplex proteins(hoop and clamp domains of TRI-1 and clamp domain of TRI-2)contribute to the formation of a mature capsid.These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attach-ing unique functional tegument proteins outside.展开更多
文摘Co-infections of the central nervous system (CNS) caused by bacterial and viral pathogens are considered to be rare. Herpes simplex virus type-1 (HSV-1) reactivation following Streptococcus pneumoniae infection is well described but most cases are related to oral or cutaneous lesions or in respiratory samples. HSV-1 CNS reactivation after Streptococcus pneumoniae meningitis is a very rare event and may have significant morbidity and mortality. In this case report, we describe a 71-year-old female patient that presented with a history of abdominal pain and confusion/disorientation that had tonic-clonic seizures while in the Emergency Department. The diagnostic work-up confirmed CNS co-infection caused by Streptococcus pneumoniae and HSV-1. Of note, beyond age, the patient had no known risk factors for both entities and recovered fully after antibiotic and antiviral therapy. This case underlines that clinicians must be aware of CNS co-infection despite being a rare diagnosis. This should be suspected particularly in patients who present an unusual clinical course of CNS infection.
基金the National Key Research and Development Program of China(2017YFC1200205 to Z.Z.and 2017YFC1200204 to D.P.).
文摘Background:Herpes simplex virus type 1(HSV-1)is a ubiquitous infectious pathogen that widely affects human health.To decipher the complicated human-HSV-1 interactions,a comprehensive protein-protein interaction(PPI)network between human and HSV-1 is highly demanded.Methods:To complement the experimental identification of human-HSV-1 PPIs,an integrative strategy to predict proteome-wide PPIs between human and HSV-1 was developed.For each human-HSV-1 protein pair,four popular PPI inference methods,including interolog mapping,the domain-domain interaction-based method,the domain-motif interaction-based method,and the machine learning-based method,were optimally implemented to generate four interaction probability scores,which were further integrated into a final probability score.Results:As a result,a comprehensive high-confidence PPI network between human and HSV-1 was established,covering 10,432 interactions between 4,546 human proteins and 72 HSV-1 proteins.Functional and network analyses of the HSV-1 targeting proteins in the context of human interactome can recapitulate the known knowledge regarding the HSV-1 replication cycle,supporting the overall reliability of the predicted PPI network.Considering that HSV-1 infections are implicated in encephalitis and neurodegenerative diseases,we focused on exploring the biological significance of the brain-specific human-HSV-1 PPIs.In particular,the predicted interactions between HSV-1 proteins and Alzheimer's-disease-related proteins were intensively investigated.Conclusion:The current work can provide testable hypotheses to assist in the mechanistic understanding of the human-HSV-1 relationship and the anti-HSV-1 pharmaceutical target discovery.To make the predicted PPI network and the datasets freely accessible to the scientific community,a user-friendly database browser was released at http://www.zzdlab.com/HintHSV/index.php.
基金Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program.
文摘BACKGROUND Herpes simplex virus(HSV)is a highly infectious pathogen that is easily transmitted via the bodily fluids of an infected individual.This virus usually affects individuals older than six months of age,and rarely causes lesions or symptoms in younger patients.CASE SUMMARY We present the case of a five-month-old healthy girl who presented with painful herpetic gingivostomatitis and perioral vesicles.We discuss the pathophysiology of primary HSV infection and the effect of maternal antibodies on the infant’s immune system.In addition,we explain the diagnosis,management,and prognosis of HSV infection in young infants.CONCLUSION This case highlights the importance of early diagnosis and management of HSV infections to decrease the risk of developing severe complications and death.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
基金Wuhan Institute of Virology for financial support for the research(grant no.EISA020201).
文摘Herpes simplex virus type 1(HSV-1)causes lifelong infections worldwide,and currently there is no efficient cure or vaccine.HSV-1-derived tools,such as neuronal circuit tracers and oncolytic viruses,have been used exten-sively;however,further genetic engineering of HSV-1 is hindered by its complex genome structure.In the present study,we designed and constructed a synthetic platform for HSV-1 based on H129-G4.The complete genome was constructed from 10 fragments through 3 rounds of synthesis using transformation-associated recombination(TAR)in yeast,and was named H129-Syn-G2.The H129-Syn-G2 genome contained two copies of the gfp gene and was transfected into cells to rescue the virus.According to growth curve assay and electron microscopy results,the synthetic viruses exhibited more optimized growth properties and similar morphogenesis compared to the parental virus.This synthetic platform will facilitate further manipulation of the HSV-1 genome for the devel-opment of neuronal circuit tracers,oncolytic viruses,and vaccines.
基金supported by grants from the State Key Development Program for Basic Research of China(973 Program)(Grant Nos.2010CB530105 and 2011CB504802)The Startup Fund of the 100 Talents Program from the Chinese Academy of Sciences(No.20072020-141)National Natural Science Foundation of China(Grant Nos.30870120,81171584,81101263,and 81000736)。
文摘Herpes simplex virus type 1(HSV-1)is a common hu-man pathogen causing cold sores and even more se-rious diseases.It can establish a latent stage in sensory ganglia after primary epithelial infections,and reacti-vate in response to stress or sunlight.Previous studies have demonstrated that viral immediate-early protein ICP0 plays a key role in regulating the balance between lytic and latent infection.Recently,It has been deter-mined that promyelocytic leukemia(PML)nuclear bod-ies(NBs),small nuclear sub-structures,contribute to the repression of HSV-1 infection in the absence of functional ICP0.In this review,we discuss the funda-mentals of the interaction between ICP0 and PML NBs,suggesting a potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1.
基金the cryoEM facility in the Electron Imaging Center for Nanomachines by NIH(1S10RR23057 to ZHZ)and CNSI at UCLA.
文摘Cytomegalovirus(CMV)is distinct among members of the Herpesviridae family for having the largest dsDNA genome(230 kb).Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid,but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described.Here,we report a cryo electron microscopy(cryoEM)structure of the murine cytomegalovirus(MCMV)capsid at a 9.1Åresolution and describe the molecular interactions among the~3000 protein molecules in the MCMV capsid at the secondary structure level.Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling.The major capsid protein(MCP)upper domain(MCPud)containsα-helices andβ-sheets conserved with those in MCPud of herpes simplex virus type 1(HSV-1),with the largest differences identifi ed as a“saddle loop”region,located at the tip of MCPud and involved in interaction with the smallest capsid protein(SCP).Interactions among the bacteriophage HK97-like fl oor domain of MCP,the middle domain of MCP,the hook and clamp domains of the triplex proteins(hoop and clamp domains of TRI-1 and clamp domain of TRI-2)contribute to the formation of a mature capsid.These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attach-ing unique functional tegument proteins outside.
