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
Quercetin is a natural compound with potent antiviral effects;however,its role in the treatment of herpes simplex keratitis(HSK)remains underexplored.Here,we investigated the antiviral effects of quercetin against her...Quercetin is a natural compound with potent antiviral effects;however,its role in the treatment of herpes simplex keratitis(HSK)remains underexplored.Here,we investigated the antiviral effects of quercetin against herpes simplex virus 1(HSV-1).By examining different phases of viral infection in human corneal epithelial cells(HCECs),we found that 30μmol/L quercetin inhibits HSV-1 replication primarily by disrupting viral attachment.RNA-sequencing and subsequent analyses revealed that the nuclear factor E2-related factor 2(Nrf2)was upregulated by quercetin in a dose-dependent manner.Knocking down Nrf2 partially compromised quercetin's antiviral effect.Importantly,topical application of 100μmol/L quercetin alleviated HSK severity in mice,reduced viral titers in tears,and inhibited VP16 expression in the cornea and trigeminal ganglia.These findings demonstrate the antiviral effect of quercetin against HSV-1 and provide a foundation for mechanistic studies to elucidate its therapeutic potential in HSK.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
Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious...Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious cell culture protein 34.5 (ICP34.5) and latency-associated transcript (LAT) genes are closely related to virus selective infection and latent infection. Their engineering is essential for constructing efficient and safe oHSV. We summarized the mechanisms of ICP34.5 and LAT in the course of HSV-1 infection and reviewed the engineered oHSVs. We are aimed to provide an insight in developing oHSV in the future.展开更多
Herpes simplex virus （HSV）, a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir （ACV） and related nucleos...Herpes simplex virus （HSV）, a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir （ACV） and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets （the DNA helicase/primase （H/P） complex）, new types of molecules （nature products） and new antiviral mechanisms （lethal mutagenesis of Janus-type nucleosides） to fight the drug resistance of HSV.展开更多
We previously constructed a herpes simplex virus 1(HSV-1) UL7 mutant virus(M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mu...We previously constructed a herpes simplex virus 1(HSV-1) UL7 mutant virus(M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mutant, we further modified the UL41 gene, which encodes another tegument protein, and the latency-associated transcript(LAT) gene. Observations of the resulting mutants with modified UL7 and UL41(M2) or UL7, UL41 and LAT(M3) genes indicated attenuated phenotypes, with lower proliferative ratios in various cells, non-lethal infections in mice and lower viral loads in nervous tissues compared with the wild-type strain. Furthermore, no LAT stable intron could be detected in the trigeminal ganglion of M3-infected animals. The results obtained with the three HSV-1 mutants indicate that the M3 mutant is an attenuated strain with low pathogenicity during both acute and latent infections. Together, the results support the use of the M3 mutant as a candidate for the development of an HSV-1 vaccine.展开更多
The herpes simplex virus type 1 （HSV-1） infected-cell protein 27 （ICP27） is an essential, highly conserved protein involved in various steps of HSV-1 gene regulation as well as in the shut-off of host gene express...The herpes simplex virus type 1 （HSV-1） infected-cell protein 27 （ICP27） is an essential, highly conserved protein involved in various steps of HSV-1 gene regulation as well as in the shut-off of host gene expression during infection. It functions primarily at the post-transcriptional level in inhibiting precursor mRNA splicing and in promoting nuclear export of viral transcripts. Recently, many novel functions performed by the HSV- 1 ICP27 protein were shown, including leptomycin B resistance, inhibition of the type I interferon signaling, regulation of the viral mRNA translation and determining the composition of HSV-1 virions展开更多
In more than half of infertile men, the cause of their infertility is unknown. Several studies revealed the role of viral infections in male infertility. The aim of the present study was to determine the prevalence of...In more than half of infertile men, the cause of their infertility is unknown. Several studies revealed the role of viral infections in male infertility. The aim of the present study was to determine the prevalence of herpes simplex virus-1 （HSV-1） and HSV-2 in semen from asymptomatic infertile male patients, and its association with altered semen parameters. A total of 70 semen samples were collected from infertile men who attended the Research and Clinical Center for Infertility in Yazd, Iran. Semen analysis and diagnostic real-time PCR using specific primers and probes for HSV-1 and HSV-2 DNA were performed. Comparison of semen parameters between virally in- fected and non-infected samples were performed with independent t-test and Mann-Whitney test. Semen analysis showed that infertile men fell into two groups, the male factor group and the unexplained group. HSV-1 and HSV-2 DNA was detected in 16 （22.9%） and 10 （14.3%） of 70 semen samples, respectively. All HSV-positive samples had abnormal semen parameters （the male factor group）. Although HSV infection was not associated with sperm motility and morphological defects, it was correlated with lower sperm count in the seminal fluid. The findings suggest that asymptomatic seminal infection of HSV plays an important role in male infertility by adversely af- fecting sperm count.展开更多
Herpes simplex virus (HSV) is a group of common human pathogens with two serotypes HSV-1 and HSV-2.The prevalence of HSV is worldwide.It primarily infects humans through epithelial cells,when it introduces a latent in...Herpes simplex virus (HSV) is a group of common human pathogens with two serotypes HSV-1 and HSV-2.The prevalence of HSV is worldwide.It primarily infects humans through epithelial cells,when it introduces a latent infection into the nervous system.During viral latency,only a region known as the latency-associated transcript (LAT) is expressed.The discovery of HSV miRNAs helps to draw a larger picture of the infection and pathogenesis of the virus.This review summarizes miRNAs found in HSV-1 and HSV-2 so far.The functional studies of miRNAs in HSV to date indicate that they play a stage-specific role coordinated with viral proteins to maintain the virus life cycle.展开更多
For over one hundred years, viruses have been recognized as capable of killing tumor cells. At present, people are still researching and constructing more suitable oncolytic viruses for treating different malignant tu...For over one hundred years, viruses have been recognized as capable of killing tumor cells. At present, people are still researching and constructing more suitable oncolytic viruses for treating different malignant tumors. Although extensive studies have demonstrated that herpes simplex virus type 1 (HSV-1) is the most potential oncolytic virus, therapies based on herpes simplex virus type 1 vectors still arouse bio-safety and risk management issues. Researchers have therefore introduced the new idea of treating cancer with HSV-1 mutants labeled with radionuclides, combining radionuclide and oncolytic virus therapies. This overview briefly summarizes the status and mechanisms by which oncolytic viruses kill tumor cells, discusses the application of HSV-1 and HSV-1 derived vectors for tumor therapy, and demonstrates the feasibility and prospect of HSV-1 mutants labeled with radionuclides for treating tumors.展开更多
Human herpesviruses （HVs） have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system （CNS）. The ability of HVs to enter a state of latency, a defining char- acteris...Human herpesviruses （HVs） have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system （CNS）. The ability of HVs to enter a state of latency, a defining char- acteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease （NDD） patholo- gy by highlighting two prominent members of the HV family, herpes simplex virus 1 （HSV-1） and human herpesvirus 6 （HHV-6）. We （i） introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then （ii） review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer＇s disease （AD） and multiple sclerosis （MS）, respectively. We then （iii） highlight and dis- cuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we （iv） discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.展开更多
Herpes simplex virus type 1 （HSV-1）, a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life includin...Herpes simplex virus type 1 （HSV-1）, a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine can- didates for HSV-I.展开更多
Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent unin...Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor （CDl18-/） are extremely sensitive to ocular infection with low doses （100 PFU） of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type （WT） controls. The enhanced susceptibil- ity correlated with a loss of CD4＋ and CD8＋ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.展开更多
As one of the immediate-early(IE)proteins of herpes simplex virus type 1(HSV-1),ICP22 is a multifunctional viral regulator that localizes in the nucleus of infected cells.It is required in experimental animal systems ...As one of the immediate-early(IE)proteins of herpes simplex virus type 1(HSV-1),ICP22 is a multifunctional viral regulator that localizes in the nucleus of infected cells.It is required in experimental animal systems and some nonhuman cell lines,but not in Vero or HEp-2 cells.ICP22 is extensively phosphorylated by viral and cellular kinases and nucleotidylylated by casein kinase Ⅱ.It has been shown to be required for efficient expression of early(E)genes and a subset of late(L)genes.ICP22,in conjunction with the UL13 kinase,mediates the phosphorylation of RNA polymerase Ⅱ.Both ICP22 and UL13 are required for the activation of cdc2,the degradation of cyclins A and B and the acquisition of a new cdc2 partner,the UL42 DNA polymerase processivity factor.The cdc2-UL42 complex mediates postranscriptional modification of topoisomerase Ⅱα in an ICP22-dependent manner to promote L gene expression.In addition,ICP22 interacts with cdk9 in a Us3 kinase dependent fashion to phosphorylate RNA polymerase Ⅱ.展开更多
Nucleoside analogues have been the mainstay of clinical treatment of herpes simplex virus 1 (HSV-1) infections since their development. However, the emergence of drug resistant strains has underlined the urgency of th...Nucleoside analogues have been the mainstay of clinical treatment of herpes simplex virus 1 (HSV-1) infections since their development. However, the emergence of drug resistant strains has underlined the urgency of the discovery of novel anti-HSV-1 drugs. Natural products, which provided many novel drug leads, are known to be an important source of anti-HSV-1 agents. Herein, we present an overview of natural products with anti-HSV-1 activities isolated from a variety of plants reported in recent years. Several different compounds, mainly belonging to the three groups of polysaccharides, polyphenols and terpenes, showed antiviral effects against HSV-1, indicating their potential to be promising anti-HSV-1 agents.展开更多
Objective:JieZe-1(JZ-1),a Chinese herbal prescription,has an obvious effect on genital herpes,which is mainly caused by herpes simplex virus type 2(HSV-2).Our study aimed to address whether HSV-2 induces pyroptosis of...Objective:JieZe-1(JZ-1),a Chinese herbal prescription,has an obvious effect on genital herpes,which is mainly caused by herpes simplex virus type 2(HSV-2).Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.Methods:HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection.Cells were co-treated with HSV-2 and penciclovir(0.078125 mg/mL)or caspase-1 inhibitor VX-765(24 h pretreatment with 100μmol/L)or JZ-1(0.078125-50 mg/mL).Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1.Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy,Hoechst 33342/propidium iodide staining,lactate dehydrogenase release assay,gene and protein expression,coimmunoprecipitation,immunofluorescence,and enzyme-linked immunosorbent assay.Results:HSV-2 induced pyroptosis of VK2/E6E7 cells,with the most significant increase observed 24 h after the infection.JZ-1 effectively inhibited HSV-2(the 50%inhibitory concentration=1.709 mg/mL),with the 6.25 mg/mL dose showing the highest efficacy(95.76%).JZ-1(6.25 mg/mL)suppressed pyroptosis of VK2/E6E7 cells.It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domaincontaining protein 3(P<0.001)and interferon-γ-inducible protein 16(P<0.001),and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain,and reducing cleaved caspase-1 p20(P<0.01),gasdermin D-N(P<0.01),interleukin(IL)-1β(P<0.001),and IL-18 levels(P<0.001).Conclusion:JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells,and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection.These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1.展开更多
HUMAN herpes simplex virus esophagitis （HSVE） was first reported in 1940 by Johnson. ^1HSVE usually occurs in immunocompromised patients,such as those with acquired immunodeficiency syndrome （AIDS）, 2-4 malignanc...HUMAN herpes simplex virus esophagitis （HSVE） was first reported in 1940 by Johnson. ^1HSVE usually occurs in immunocompromised patients,such as those with acquired immunodeficiency syndrome （AIDS）, 2-4 malignancies, cutaneous burns, connective tissue diseases, inflammatory bowel disease, those taking immuno-suppressive therapy, and those undergoing organ transplantation,5 etc. In the immunocompetent individuals, HSVE is rare, having been reported in 39 cases and mainly affecting young males^6,7 The aim of this study was to delineate the clinical experience in the diagnosis of HSVE using rapid in situ hybridization and assess the various detection methods.展开更多
AIM： To explore the therapeutic efficacy and mechanism of herpes simplex virus-thymidine kinase （HSV-tk） targeting angiogenesis against hepatocellular carcinoma in vivio and in vitro. METHODS： Recombinant adenovir...AIM： To explore the therapeutic efficacy and mechanism of herpes simplex virus-thymidine kinase （HSV-tk） targeting angiogenesis against hepatocellular carcinoma in vivio and in vitro. METHODS： Recombinant adenovirus containing kinase domain insert with receptor （KDR） or cytomegalovirus （CMV） promoter-controlled HSV-tk gene （AdKDR-tk and AdCMV-tk） was constructed using pAdeasy system. The expression of KDR antigen in human umbilical venous endothelial cells （HUVEC） and HepG2 was detected with histological analysis of cells. The virus was used to infect HUVEC and HepG2. Following administration of ganciclovir （GCV）, the survival rate of gene-transfected HUVEC and HepG2 was evaluated by MTT method. To develop hepatocarcinomas in 32 Balb/C mice with HepG2 cells, the mice were divided into four groups： ganciclovir group （Ⅰ）, Ad group （Ⅱ）, AdCMV-tk group （Ⅲ） and AdKDR-tk group （Ⅳ）. Then selective administration of recombinant adenovirus or Ad via the intratumorial was given to all rats. Ganciclovir （GCV） was given at a dose of 100 mg·kg^-1·d^-1 （ip） started on the following day and lasted 10 d. Microvessel density （MVD） of tumor in all the treated animals were examined by the immunohistochemical methods and tumor burden was evaluated 10 d before and alter the last GCV dose.RESULTS： Immunocytochemical staining indicated the expression of KDR antigen in HUVEC. Under adenovirus infection index of 100, with increasing GCV concentration from 0 up to 50 mg/L, the survival rate of AdKDR-tk- transfected HUVEC and HepG2 decreased from 100% to （28.94 ± 5.67）% and （75.45 ± 2.91）% at proper order, respectively （P 〈 0.01）, while the survival rate of AdCMV- tk-transfected HUVEC and HepG2 declined from 100% to （17.56 ± 2.48）% and （23.15± 5.72）%, respectively （P 〉 0.05）. Compared with group I, there was a decrease of tumor weight by 14.7% in group Ⅲ and by 23.6% in group Ⅳ. And there was a distinct difference between group M and Ⅳ （P 〈 0.05）. The median MVD for all groups was 37.4 ± 8.6, 30.6 ± 7.8, 27.6 ± 7.1, and 10.7 ± 4.1 （microvessels/mm^2） in group Ⅰ, Ⅱ, M and IV, respectively. And there was a marked difference between group M and Ⅱ （P 〈 0.05）, Ⅳ and Ⅱ （P 〈 0.01）, and Ⅳ and M （P 〈 0.01）. CONCLUSION： KDR promoter-HSV-tk gene may effectually restrain the growth of tumor via targeting angiogenesis for hepatocellular carcinoma with treatment of GCV.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
AIM:To investigate the effect of Staphylococcus aureus(S.aures)lysates(SALs)on herpes simplex virus type-Ⅰ(HSV1)infection in human corneal epithelial(HCE)cells and in a mouse model of HSV1 keratitis.METHODS:HCE,Vero,...AIM:To investigate the effect of Staphylococcus aureus(S.aures)lysates(SALs)on herpes simplex virus type-Ⅰ(HSV1)infection in human corneal epithelial(HCE)cells and in a mouse model of HSV1 keratitis.METHODS:HCE,Vero,HeLa,and BV2 cells were infected with HSV1[HSV1f strain,HSV1f;HSV-1-H129 with green fluorescent protein(GFP)knock-in,HSV1g].Pre-or post-infection,SAL at various concentrations was added to the culture medium for 24 h.GFP fluorescence in HSV1g or plaque formation by HSV1f were examined.The effects of heat-treated SAL,precooled acetone-precipitated SAL,and SAL subjected to ultrafiltration(100 kDa)were evaluated.The effects of other bacterial components and lysates on HSV1 infection were also tested,including lipoteichoic acid(LTA),peptidoglycan(PGN),staphylococcal protein A(SPA),andα-hemolysin from S.aureus(α-toxin)as well as lysates from a wild-type S.aureus strain,S.epidermidis,and Escherichia coli(W-SAL,SEL,and ECL,respectively).In addition,SAL eye drops were applied topically to BALB/c mice with HSV1 keratitis,followed by in vivo observations.RESULTS:The cytopathic effect,plaque formation(HSV1f),and GFP expression(HSV1g)in infected cells were inhibited by SAL in a dose-dependent manner.The active component of SAL(≥100 kDa)was heat-sensitive and retained activity after acetone precipitation.In HSV1ginfected cells,treatment with LTA-sa,α-toxin,PGN-sa,or SPA did not inhibit GFP expression.SAL,W-SAL,and SEL(but not ECL)decreased GFP expression.In mice with HSV1 keratitis,SAL reduced corneal lesions by 71%.CONCLUSION:The results of this study demonstrate that SAL can be used to inhibit HSV1 infection,particularly keratitis.Further studies are needed to determine the active components and mechanism underlying the effects of SAL.展开更多
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supported by the National Natural Science Foundation of China(No.81970848).
文摘Quercetin is a natural compound with potent antiviral effects;however,its role in the treatment of herpes simplex keratitis(HSK)remains underexplored.Here,we investigated the antiviral effects of quercetin against herpes simplex virus 1(HSV-1).By examining different phases of viral infection in human corneal epithelial cells(HCECs),we found that 30μmol/L quercetin inhibits HSV-1 replication primarily by disrupting viral attachment.RNA-sequencing and subsequent analyses revealed that the nuclear factor E2-related factor 2(Nrf2)was upregulated by quercetin in a dose-dependent manner.Knocking down Nrf2 partially compromised quercetin's antiviral effect.Importantly,topical application of 100μmol/L quercetin alleviated HSK severity in mice,reduced viral titers in tears,and inhibited VP16 expression in the cornea and trigeminal ganglia.These findings demonstrate the antiviral effect of quercetin against HSV-1 and provide a foundation for mechanistic studies to elucidate its therapeutic potential in HSK.
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.
文摘Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious cell culture protein 34.5 (ICP34.5) and latency-associated transcript (LAT) genes are closely related to virus selective infection and latent infection. Their engineering is essential for constructing efficient and safe oHSV. We summarized the mechanisms of ICP34.5 and LAT in the course of HSV-1 infection and reviewed the engineered oHSVs. We are aimed to provide an insight in developing oHSV in the future.
基金the National Natural Science Foundations of China(document no.:81321002,81500860,81300888)a grant from 111 Project of Ministry of Education,China,for fi nancial support
文摘Herpes simplex virus （HSV）, a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir （ACV） and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets （the DNA helicase/primase （H/P） complex）, new types of molecules （nature products） and new antiviral mechanisms （lethal mutagenesis of Janus-type nucleosides） to fight the drug resistance of HSV.
基金supported by the National Basic Research Program (2012CB518901)Chinese academy of medical sciences (CAMS) Initiative for Innovative Medicine (2016I2M-1-019)+1 种基金the National Natural Science Foundation of China (31300143, 31100127)the Fundamental Research Funds for the Central Universities (2016ZX310047, 2016ZX350072)
文摘We previously constructed a herpes simplex virus 1(HSV-1) UL7 mutant virus(M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mutant, we further modified the UL41 gene, which encodes another tegument protein, and the latency-associated transcript(LAT) gene. Observations of the resulting mutants with modified UL7 and UL41(M2) or UL7, UL41 and LAT(M3) genes indicated attenuated phenotypes, with lower proliferative ratios in various cells, non-lethal infections in mice and lower viral loads in nervous tissues compared with the wild-type strain. Furthermore, no LAT stable intron could be detected in the trigeminal ganglion of M3-infected animals. The results obtained with the three HSV-1 mutants indicate that the M3 mutant is an attenuated strain with low pathogenicity during both acute and latent infections. Together, the results support the use of the M3 mutant as a candidate for the development of an HSV-1 vaccine.
基金Start Fund of the Hundred Talents Program of the Chinese Academy of Science (20071010-141)National Natural Science Foundation of China(30870120)Open Research Fund Program of the State Key Laboratory of Virology of China (2007003)
文摘The herpes simplex virus type 1 （HSV-1） infected-cell protein 27 （ICP27） is an essential, highly conserved protein involved in various steps of HSV-1 gene regulation as well as in the shut-off of host gene expression during infection. It functions primarily at the post-transcriptional level in inhibiting precursor mRNA splicing and in promoting nuclear export of viral transcripts. Recently, many novel functions performed by the HSV- 1 ICP27 protein were shown, including leptomycin B resistance, inhibition of the type I interferon signaling, regulation of the viral mRNA translation and determining the composition of HSV-1 virions
基金supported by Tehran University of Medical Sciences(No.P/943)
文摘In more than half of infertile men, the cause of their infertility is unknown. Several studies revealed the role of viral infections in male infertility. The aim of the present study was to determine the prevalence of herpes simplex virus-1 （HSV-1） and HSV-2 in semen from asymptomatic infertile male patients, and its association with altered semen parameters. A total of 70 semen samples were collected from infertile men who attended the Research and Clinical Center for Infertility in Yazd, Iran. Semen analysis and diagnostic real-time PCR using specific primers and probes for HSV-1 and HSV-2 DNA were performed. Comparison of semen parameters between virally in- fected and non-infected samples were performed with independent t-test and Mann-Whitney test. Semen analysis showed that infertile men fell into two groups, the male factor group and the unexplained group. HSV-1 and HSV-2 DNA was detected in 16 （22.9%） and 10 （14.3%） of 70 semen samples, respectively. All HSV-positive samples had abnormal semen parameters （the male factor group）. Although HSV infection was not associated with sperm motility and morphological defects, it was correlated with lower sperm count in the seminal fluid. The findings suggest that asymptomatic seminal infection of HSV plays an important role in male infertility by adversely af- fecting sperm count.
基金supported by the National Natural Sciences Foundation of China(No.30670094 and 30700028)Youth Science Research Foundation of PUMC(No.2012X23)
文摘Herpes simplex virus (HSV) is a group of common human pathogens with two serotypes HSV-1 and HSV-2.The prevalence of HSV is worldwide.It primarily infects humans through epithelial cells,when it introduces a latent infection into the nervous system.During viral latency,only a region known as the latency-associated transcript (LAT) is expressed.The discovery of HSV miRNAs helps to draw a larger picture of the infection and pathogenesis of the virus.This review summarizes miRNAs found in HSV-1 and HSV-2 so far.The functional studies of miRNAs in HSV to date indicate that they play a stage-specific role coordinated with viral proteins to maintain the virus life cycle.
基金National Natural Science Foundation of China, No. 30770604
文摘For over one hundred years, viruses have been recognized as capable of killing tumor cells. At present, people are still researching and constructing more suitable oncolytic viruses for treating different malignant tumors. Although extensive studies have demonstrated that herpes simplex virus type 1 (HSV-1) is the most potential oncolytic virus, therapies based on herpes simplex virus type 1 vectors still arouse bio-safety and risk management issues. Researchers have therefore introduced the new idea of treating cancer with HSV-1 mutants labeled with radionuclides, combining radionuclide and oncolytic virus therapies. This overview briefly summarizes the status and mechanisms by which oncolytic viruses kill tumor cells, discusses the application of HSV-1 and HSV-1 derived vectors for tumor therapy, and demonstrates the feasibility and prospect of HSV-1 mutants labeled with radionuclides for treating tumors.
文摘Human herpesviruses （HVs） have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system （CNS）. The ability of HVs to enter a state of latency, a defining char- acteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease （NDD） patholo- gy by highlighting two prominent members of the HV family, herpes simplex virus 1 （HSV-1） and human herpesvirus 6 （HHV-6）. We （i） introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then （ii） review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer＇s disease （AD） and multiple sclerosis （MS）, respectively. We then （iii） highlight and dis- cuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we （iv） discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.
基金supported by the Wuhan Institute of Virology (WIV) “One-Three-Five” Strategic Programs,China
文摘Herpes simplex virus type 1 （HSV-1）, a neurotropic member of the alphaherpes virus family, is among the most prevalent and successful human pathogens. HSV-1 can cause serious diseases at every stage of life including fatal disseminated disease in newborns, cold sores, eye disease, and fatal encephalitis in adults. HSV-1 infection can trigger rapid immune responses, and efficient inhibition and clearance of HSV-1 infection rely on both the innate and adaptive immune responses of the host. Multiple strategies have been used to restrict host innate immune responses by HSV-1 to facilitate its infection in host cells. The adaptive immunity of the host plays an important role in inhibiting HSV-1 infections. The activation and regulation of T cells are the important aspects of the adaptive immunity. They play a crucial role in host-mediated immunity and are important for clearing HSV-1. In this review, we examine the findings on T cell immune responses during HSV-1 infection, which hold promise in the design of new vaccine can- didates for HSV-I.
基金supported by USPHS grant (No. AI053108) to DanielJ.J. CarrP20 (No. RR017703)+1 种基金an unrestricted grant from Research to Prevent Blindnesssupported by NIAID training grant(No. AI007633)
文摘Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor （CDl18-/） are extremely sensitive to ocular infection with low doses （100 PFU） of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type （WT） controls. The enhanced susceptibil- ity correlated with a loss of CD4＋ and CD8＋ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.
基金The Startup Fund of the Hundred Talents Program of the Chinese Academy of Science(20071010141)National Natural Science Foundation of China (30870120)+1 种基金Open Research Fund Program of the State Key Laboratory of Virology of China(2007003,2009 007)Hubei Province Natural Science Foundation of Innovation Groups Project(2008CDA013)
文摘As one of the immediate-early(IE)proteins of herpes simplex virus type 1(HSV-1),ICP22 is a multifunctional viral regulator that localizes in the nucleus of infected cells.It is required in experimental animal systems and some nonhuman cell lines,but not in Vero or HEp-2 cells.ICP22 is extensively phosphorylated by viral and cellular kinases and nucleotidylylated by casein kinase Ⅱ.It has been shown to be required for efficient expression of early(E)genes and a subset of late(L)genes.ICP22,in conjunction with the UL13 kinase,mediates the phosphorylation of RNA polymerase Ⅱ.Both ICP22 and UL13 are required for the activation of cdc2,the degradation of cyclins A and B and the acquisition of a new cdc2 partner,the UL42 DNA polymerase processivity factor.The cdc2-UL42 complex mediates postranscriptional modification of topoisomerase Ⅱα in an ICP22-dependent manner to promote L gene expression.In addition,ICP22 interacts with cdk9 in a Us3 kinase dependent fashion to phosphorylate RNA polymerase Ⅱ.
基金Joint funds of National Natural Science Foundation of China (U0632010)
文摘Nucleoside analogues have been the mainstay of clinical treatment of herpes simplex virus 1 (HSV-1) infections since their development. However, the emergence of drug resistant strains has underlined the urgency of the discovery of novel anti-HSV-1 drugs. Natural products, which provided many novel drug leads, are known to be an important source of anti-HSV-1 agents. Herein, we present an overview of natural products with anti-HSV-1 activities isolated from a variety of plants reported in recent years. Several different compounds, mainly belonging to the three groups of polysaccharides, polyphenols and terpenes, showed antiviral effects against HSV-1, indicating their potential to be promising anti-HSV-1 agents.
基金supported by grants from the National Natural Science Foundation of China (No. 81874483)
文摘Objective:JieZe-1(JZ-1),a Chinese herbal prescription,has an obvious effect on genital herpes,which is mainly caused by herpes simplex virus type 2(HSV-2).Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.Methods:HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection.Cells were co-treated with HSV-2 and penciclovir(0.078125 mg/mL)or caspase-1 inhibitor VX-765(24 h pretreatment with 100μmol/L)or JZ-1(0.078125-50 mg/mL).Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1.Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy,Hoechst 33342/propidium iodide staining,lactate dehydrogenase release assay,gene and protein expression,coimmunoprecipitation,immunofluorescence,and enzyme-linked immunosorbent assay.Results:HSV-2 induced pyroptosis of VK2/E6E7 cells,with the most significant increase observed 24 h after the infection.JZ-1 effectively inhibited HSV-2(the 50%inhibitory concentration=1.709 mg/mL),with the 6.25 mg/mL dose showing the highest efficacy(95.76%).JZ-1(6.25 mg/mL)suppressed pyroptosis of VK2/E6E7 cells.It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domaincontaining protein 3(P<0.001)and interferon-γ-inducible protein 16(P<0.001),and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain,and reducing cleaved caspase-1 p20(P<0.01),gasdermin D-N(P<0.01),interleukin(IL)-1β(P<0.001),and IL-18 levels(P<0.001).Conclusion:JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells,and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection.These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1.
文摘HUMAN herpes simplex virus esophagitis （HSVE） was first reported in 1940 by Johnson. ^1HSVE usually occurs in immunocompromised patients,such as those with acquired immunodeficiency syndrome （AIDS）, 2-4 malignancies, cutaneous burns, connective tissue diseases, inflammatory bowel disease, those taking immuno-suppressive therapy, and those undergoing organ transplantation,5 etc. In the immunocompetent individuals, HSVE is rare, having been reported in 39 cases and mainly affecting young males^6,7 The aim of this study was to delineate the clinical experience in the diagnosis of HSVE using rapid in situ hybridization and assess the various detection methods.
基金Supported by the National Natural Science Foundation of China, No. 30371386the Natural Science Foundation of Guangdong Province, No. 31010
文摘AIM： To explore the therapeutic efficacy and mechanism of herpes simplex virus-thymidine kinase （HSV-tk） targeting angiogenesis against hepatocellular carcinoma in vivio and in vitro. METHODS： Recombinant adenovirus containing kinase domain insert with receptor （KDR） or cytomegalovirus （CMV） promoter-controlled HSV-tk gene （AdKDR-tk and AdCMV-tk） was constructed using pAdeasy system. The expression of KDR antigen in human umbilical venous endothelial cells （HUVEC） and HepG2 was detected with histological analysis of cells. The virus was used to infect HUVEC and HepG2. Following administration of ganciclovir （GCV）, the survival rate of gene-transfected HUVEC and HepG2 was evaluated by MTT method. To develop hepatocarcinomas in 32 Balb/C mice with HepG2 cells, the mice were divided into four groups： ganciclovir group （Ⅰ）, Ad group （Ⅱ）, AdCMV-tk group （Ⅲ） and AdKDR-tk group （Ⅳ）. Then selective administration of recombinant adenovirus or Ad via the intratumorial was given to all rats. Ganciclovir （GCV） was given at a dose of 100 mg·kg^-1·d^-1 （ip） started on the following day and lasted 10 d. Microvessel density （MVD） of tumor in all the treated animals were examined by the immunohistochemical methods and tumor burden was evaluated 10 d before and alter the last GCV dose.RESULTS： Immunocytochemical staining indicated the expression of KDR antigen in HUVEC. Under adenovirus infection index of 100, with increasing GCV concentration from 0 up to 50 mg/L, the survival rate of AdKDR-tk- transfected HUVEC and HepG2 decreased from 100% to （28.94 ± 5.67）% and （75.45 ± 2.91）% at proper order, respectively （P 〈 0.01）, while the survival rate of AdCMV- tk-transfected HUVEC and HepG2 declined from 100% to （17.56 ± 2.48）% and （23.15± 5.72）%, respectively （P 〉 0.05）. Compared with group I, there was a decrease of tumor weight by 14.7% in group Ⅲ and by 23.6% in group Ⅳ. And there was a distinct difference between group M and Ⅳ （P 〈 0.05）. The median MVD for all groups was 37.4 ± 8.6, 30.6 ± 7.8, 27.6 ± 7.1, and 10.7 ± 4.1 （microvessels/mm^2） in group Ⅰ, Ⅱ, M and IV, respectively. And there was a marked difference between group M and Ⅱ （P 〈 0.05）, Ⅳ and Ⅱ （P 〈 0.01）, and Ⅳ and M （P 〈 0.01）. CONCLUSION： KDR promoter-HSV-tk gene may effectually restrain the growth of tumor via targeting angiogenesis for hepatocellular carcinoma with treatment of GCV.
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the National Natural Science Foundation of China(No.81770896,No.81970848)the Guangzhou Science Technology and Innovation Commission(No.201607020011)。
文摘AIM:To investigate the effect of Staphylococcus aureus(S.aures)lysates(SALs)on herpes simplex virus type-Ⅰ(HSV1)infection in human corneal epithelial(HCE)cells and in a mouse model of HSV1 keratitis.METHODS:HCE,Vero,HeLa,and BV2 cells were infected with HSV1[HSV1f strain,HSV1f;HSV-1-H129 with green fluorescent protein(GFP)knock-in,HSV1g].Pre-or post-infection,SAL at various concentrations was added to the culture medium for 24 h.GFP fluorescence in HSV1g or plaque formation by HSV1f were examined.The effects of heat-treated SAL,precooled acetone-precipitated SAL,and SAL subjected to ultrafiltration(100 kDa)were evaluated.The effects of other bacterial components and lysates on HSV1 infection were also tested,including lipoteichoic acid(LTA),peptidoglycan(PGN),staphylococcal protein A(SPA),andα-hemolysin from S.aureus(α-toxin)as well as lysates from a wild-type S.aureus strain,S.epidermidis,and Escherichia coli(W-SAL,SEL,and ECL,respectively).In addition,SAL eye drops were applied topically to BALB/c mice with HSV1 keratitis,followed by in vivo observations.RESULTS:The cytopathic effect,plaque formation(HSV1f),and GFP expression(HSV1g)in infected cells were inhibited by SAL in a dose-dependent manner.The active component of SAL(≥100 kDa)was heat-sensitive and retained activity after acetone precipitation.In HSV1ginfected cells,treatment with LTA-sa,α-toxin,PGN-sa,or SPA did not inhibit GFP expression.SAL,W-SAL,and SEL(but not ECL)decreased GFP expression.In mice with HSV1 keratitis,SAL reduced corneal lesions by 71%.CONCLUSION:The results of this study demonstrate that SAL can be used to inhibit HSV1 infection,particularly keratitis.Further studies are needed to determine the active components and mechanism underlying the effects of SAL.
