目的:研究活血通络汤对家兔激素性股骨头缺血性坏死造模过程中Notch1、DLL3和HERP1的影响。方法:将192只日本大耳兔随机分为预防治疗组(A组)、治疗组(B组)、模型对照组(C组)、空白对照组(D组),每组48只,A、B、C组运用贺西京造模法造模。...目的:研究活血通络汤对家兔激素性股骨头缺血性坏死造模过程中Notch1、DLL3和HERP1的影响。方法:将192只日本大耳兔随机分为预防治疗组(A组)、治疗组(B组)、模型对照组(C组)、空白对照组(D组),每组48只,A、B、C组运用贺西京造模法造模。A组第2周开始喂服中药饲料,B组第3周开始喂服中药饲料,C、D组均喂服等量普通饲料。于第2、5、8周末检测血Notch1、DLL3和HERP1 m RNA表达水平,同时做股骨头病理镜检,计算空骨陷窝率。结果:Notch1、DLL3和HERP1表达值各组间比较不同时间段分析及空骨陷窝率分析具有统计学意义(P<0.05,P<0.01)。结论:活血通络汤可限制Notch1和HERP1的表达,下调DLL3表达水平,降低空骨陷窝率,促进骨坏死的修复。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-1 (HSV-1) remains a leading cause of viral disease worldwide and is spread by direct contact with infected lesions. There is no vaccine against HSV-1 infections and there remains a need to identif...Herpes simplex virus-1 (HSV-1) remains a leading cause of viral disease worldwide and is spread by direct contact with infected lesions. There is no vaccine against HSV-1 infections and there remains a need to identify therapeutics that could reduce the spread. In this study various hispolon compounds were analyzed to determine their antiviral potential against HSV-1 infections in cultured Vero cells. To determine the effects on infectivity and possible mechanisms of inhibition, the following assays were conducted. In vitro cytotoxicity assays were conducted to determine the effect of the compounds on cell viability and the maximum non-cytotoxic concentrations. Antiviral assays measured cell viability, percent inhibition of infection following treatment with the compounds, and the effect on the viral infection cycle. These effects were visualized using inverted light and fluorescent microscopy. Of the 24 hispolons tested, only hispolon pyrazole-1 (HISP-1) demonstrated antiviral effects. HISP-1 was demonstrated to effect early stages in HSV-1 infection in cultured Vero cells (attachment, penetration, and post-penetration). In silico modeling analyses were conducted to analyze the interactions between HISP-1 and viral glycoprotein D (gD). HISP-1 is safe at concentrations tested and is effective in inhibiting infection of HSV-1 in cultured cells. HISP-1 has potential for therapeutic use as an antiviral against HSV-1 infection, could work in synergy with other antivirals that work be a different modality, and could be developed as a component of a topical agent to reduce the spread of HSV-1 infections.展开更多
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
To investigate the inhibitory effects of Ginsenoside Rbl (GRbl) on apoptosis caused by Herpes Simplex Virus-1 (HSV-1) in Human Glioma Cells (U251), U251 cells were infected by HSV-1 at a multiplicity of infectio...To investigate the inhibitory effects of Ginsenoside Rbl (GRbl) on apoptosis caused by Herpes Simplex Virus-1 (HSV-1) in Human Glioma Cells (U251), U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRbl, GRbl+HSV-1, HSV-1 and control groups. MTT and cell apoptosis assays were used to detect the inhibitory effects of GRbl on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay. We found that in the 400 μg/mL GRb 1 and 400 μg/mL GRbl+HSV-1 groups, MTT values were higher than control group at all times (P〈0.05). Moreover, the apoptosis rate in the 400 μg/mL GRbl+HSV-1 group was lower than the HSV-1 group (P〈0. 05). These results confirmed that, at appropriate concentrations, GRbl could inhibit nerve cell apoptosis in HSV-1 infections.展开更多
AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of...AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.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
In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic ...In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CV-N on HSV-1 in Vero cells.The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR).The results showed that CV-N had a low cytotoxicity on Vero cells with a CC50 of 359.03±0.56 μg/mL,and that it could not directly inactivate HSV-1 infectivity.CV-N not only reduced the CPE of HSV-1 when added before or after viral infection,with a 50% inhibitory concentration (IC50) with 2.26 and 30.16μg/mL respectively,but it also decreased the copies of HSV-1 DNA in infected host cells.The encephalitis model for HSV-1 infection was conducted in Kunming mice,and treated with three dosages of CV-N (0.5,5 & 10 mg/kg) which was administered intraperitoneally at 2h,3d,5d,7d post infection.The duration for the appearance of symptoms of encephalitis and the survival days were recorded and brain tissue samples were obtained for pathological examination (HE staining).Compared with the untreated control group,in the 5mg/kg CV-N and 10mg/kg CV-N treated groups,the mice suffered light symptoms and the number of survival days were more than 9d and 14d respectively.HE staining also showed that in 5mg/kg CV-N and 10mg/kg CV-N treated groups,the brain cells did not show visible changes,except for a slight inflammation.Our results demonstrated that CV-N has pronounced antiviral activity against HSV-1 both in vitro and in vivo,and it would be a promising new candidate for anti-HSV therapeutics.展开更多
Herpes simplex virus type-1 (HSV-1) is one of many pathogens that use the cell surface glycosaminoglycan heparan sulfate as a receptor. Heparan sulfate is highly expressed on the surface and extracellular matrix of vi...Herpes simplex virus type-1 (HSV-1) is one of many pathogens that use the cell surface glycosaminoglycan heparan sulfate as a receptor. Heparan sulfate is highly expressed on the surface and extracellular matrix of virtually all cell types making it an ideal receptor. Heparan sulfate interacts with HSV-1 envelope glycoproteins gB and gC during the initial attachment step during HSV-1 entry. In addition,a modified form of heparan sulfate,known as 3-O-sulfated heparan sulfate,interacts with HSV-1 gD to induce fusion between the viral envelope and host cell membrane. The 3-O-sulfation of heparan sulfate is a rare modification which occurs during the biosynthesis of heparan sulfate that is carried out by a family of enzymes known as 3-O-sulfotransferases. Due to its involvement in multiple steps of the infection process,heparan sulfate has been a prime target for the development of agents to inhibit HSV entry. Understanding how heparan sulfate functions during HSV-1 infection may not only be critical for inhibiting infection by this virus,but it may also be crucial in the fight against many other pathogens as well.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
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
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
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
RNA interference (RNAi) is a process by which introduced small interfering RNA (siRNA) can cause the specific degradation of mRNA with identical sequences. The human herpes simplex virus type 1 (HSV-1) RR is composed ...RNA interference (RNAi) is a process by which introduced small interfering RNA (siRNA) can cause the specific degradation of mRNA with identical sequences. The human herpes simplex virus type 1 (HSV-1) RR is composed of two distinct homodimeric subunits encoded by UL39 and UL40,respectively. In this study,we applied siRNAs targeting the UL39 and UL40 genes of HSV-1. We showed that synthetic siRNA silenced effectively and specifically UL39 and UL40 mRNA expression and inhibited HSV-1 replication. Our work offers new possibilities for RNAi as a genetic tool for inhibition of HSV-1 replication.展开更多
AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1(HSV-1) glycoprotein C(g C) and glycoprotein D(g D) will achieve better protective effect against herpes simplex keratitis(HSK) than DNA ...AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1(HSV-1) glycoprotein C(g C) and glycoprotein D(g D) will achieve better protective effect against herpes simplex keratitis(HSK) than DNA vaccine encoding gD alone. METHODS: DNA vaccine expressing gD or gC combined g D(g D.g C) were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293 T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2 wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS: Fusion protein g D.g C could be expressed successfully in cultured 293 T cells. And, p RSC-g C.g DIL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and s Ig A production, enhanced cytotoxicities of splenocytes and nature killer cells(NK),when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION: gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.展开更多
Nuclear proteins often form punctiform structures, but the precise mechanism for this process is unknown. As a preliminary study, we investigated the aggregation of an HSV-1 immediate-early protein, infected-cell prot...Nuclear proteins often form punctiform structures, but the precise mechanism for this process is unknown. As a preliminary study, we investigated the aggregation of an HSV-1 immediate-early protein, infected-cell protein 22 (ICP22), in the nucleus by observing the localization of ICP22-EGFP fusion protein Results showed that, in high-level expression conditions, ICP22-EGFP gradually concentrates in the nucleus, persists throughout the cell cycle without disaggregation even in the cell division phase, and is finally distributed to daughter cells. We subsequently constructed a mammalian cell expression system, which had tetracycline- dependent transcriptional regulators. Consequently, the location of ICP22-EGFP in the nucleus changed with distinct induction conditions. This suggests that the cellular location of ICP22 is also influenced by promoter regulation, in addition to its own structure. Our findings provide new clues for the investigation of transcriptional regulation of viral genes. In addition, the non-protease reporter system we constructed could be utilized to evaluate the role of intemal ribosome entry sites (IRES) on transcriptional regulation.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
The protein HTRP (human transcription regulator protein) is encoded by the differential gene htrp and induced by Herpes simplex virus type 1 (HSV-1) infection in KMB-17 cells.HTRP was found to interact with SAP30 (mSi...The protein HTRP (human transcription regulator protein) is encoded by the differential gene htrp and induced by Herpes simplex virus type 1 (HSV-1) infection in KMB-17 cells.HTRP was found to interact with SAP30 (mSin3A Association Protein),one of the components of co-repressor complex mSin3A,which is part of the deacetylation transfer enzyme HDAC.To reveal the biological significance of the interaction between HTRP and SAP30,real-time PCR and a dual-luciferase detecting system was used.The results indicate that HTRP could inhibit the transcription of a viral promoter,whose interaction with SAP30 synergistically affects transcriptional inhibition of the viral genes,and is related to HDAC enzyme activity.ChIP experiments demonstrate that HTRP could promote HDAC activity by increasing the deacetylation level of lysine 14 and lysine 9 in histone H3.展开更多
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive loss of cognitive functions in affected individuals. Brain tissue pathology is associated with the formation of senile plaques ...Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive loss of cognitive functions in affected individuals. Brain tissue pathology is associated with the formation of senile plaques which result from the over-production of amyloid </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> (A</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">), due to the cleavage of a membrane bound glycoprotein. It is unclear what causes AD and its associated pathologies, but age and genetic predisposition play an import role in the likelihood of disease development. Studies have shown that the reactivation of latent herpes simplex virus 1 (HSV-1) infection can lead to the neuropathy of acute herpes simplex encephalitis (HSE), which causes similar symptoms to AD. HSV-1 infection is a known risk factor for the development of AD, but no study has determined a definitive causal relationship. Using the Qiagen In</span><span style="font-family:Verdana;">genuity Pathway Analysis (IPA) tool, the inhibitory relationship between therapeutic</span><span style="font-family:Verdana;">s for AD and HSV-1 were explored. Thirteen drugs developed to decrease A</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> buildup in AD and 32 drugs that act as HSV antivirals were retrieved from the data in the Qiagen Knowledge Base. These drugs were analyzed displayed as two separate networks. While many promising A</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> aggregation-targeting drugs have been discontinued due to lack of efficacy, HSV drugs could serve as potential therapeutics for those with AD. This review aims to describe new insights on how HSV-1 relates to the development of AD and highlight the mechanism of action of A</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-related drugs and HSV drugs in the context of AD. With HSV-1 being a likely candidate for the causation of AD, there is a need to study the effects of HSV antiviral drugs on those who have AD.展开更多
文摘目的:研究活血通络汤对家兔激素性股骨头缺血性坏死造模过程中Notch1、DLL3和HERP1的影响。方法:将192只日本大耳兔随机分为预防治疗组(A组)、治疗组(B组)、模型对照组(C组)、空白对照组(D组),每组48只,A、B、C组运用贺西京造模法造模。A组第2周开始喂服中药饲料,B组第3周开始喂服中药饲料,C、D组均喂服等量普通饲料。于第2、5、8周末检测血Notch1、DLL3和HERP1 m RNA表达水平,同时做股骨头病理镜检,计算空骨陷窝率。结果:Notch1、DLL3和HERP1表达值各组间比较不同时间段分析及空骨陷窝率分析具有统计学意义(P<0.05,P<0.01)。结论:活血通络汤可限制Notch1和HERP1的表达,下调DLL3表达水平,降低空骨陷窝率,促进骨坏死的修复。
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.
文摘Herpes simplex virus-1 (HSV-1) remains a leading cause of viral disease worldwide and is spread by direct contact with infected lesions. There is no vaccine against HSV-1 infections and there remains a need to identify therapeutics that could reduce the spread. In this study various hispolon compounds were analyzed to determine their antiviral potential against HSV-1 infections in cultured Vero cells. To determine the effects on infectivity and possible mechanisms of inhibition, the following assays were conducted. In vitro cytotoxicity assays were conducted to determine the effect of the compounds on cell viability and the maximum non-cytotoxic concentrations. Antiviral assays measured cell viability, percent inhibition of infection following treatment with the compounds, and the effect on the viral infection cycle. These effects were visualized using inverted light and fluorescent microscopy. Of the 24 hispolons tested, only hispolon pyrazole-1 (HISP-1) demonstrated antiviral effects. HISP-1 was demonstrated to effect early stages in HSV-1 infection in cultured Vero cells (attachment, penetration, and post-penetration). In silico modeling analyses were conducted to analyze the interactions between HISP-1 and viral glycoprotein D (gD). HISP-1 is safe at concentrations tested and is effective in inhibiting infection of HSV-1 in cultured cells. HISP-1 has potential for therapeutic use as an antiviral against HSV-1 infection, could work in synergy with other antivirals that work be a different modality, and could be developed as a component of a topical agent to reduce the spread of HSV-1 infections.
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Supported by National Natural Science Foundation of China(Grant No.81070501 and 30770105)Shandong Provincial Outstanding Medical Academic Professional Program
文摘To investigate the inhibitory effects of Ginsenoside Rbl (GRbl) on apoptosis caused by Herpes Simplex Virus-1 (HSV-1) in Human Glioma Cells (U251), U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRbl, GRbl+HSV-1, HSV-1 and control groups. MTT and cell apoptosis assays were used to detect the inhibitory effects of GRbl on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay. We found that in the 400 μg/mL GRb 1 and 400 μg/mL GRbl+HSV-1 groups, MTT values were higher than control group at all times (P〈0.05). Moreover, the apoptosis rate in the 400 μg/mL GRbl+HSV-1 group was lower than the HSV-1 group (P〈0. 05). These results confirmed that, at appropriate concentrations, GRbl could inhibit nerve cell apoptosis in HSV-1 infections.
基金Supported by National Natural Science Foundation of China(No.81273212,81100651)Project of Science and Technology of Shandong Province(No.2014GSF118044)
文摘AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
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Science and Technology Development Project of Shandong province (2005GG3202068)
文摘In this study,a standard strain of HSV-1 (strain SM44) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo.Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CV-N on HSV-1 in Vero cells.The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR).The results showed that CV-N had a low cytotoxicity on Vero cells with a CC50 of 359.03±0.56 μg/mL,and that it could not directly inactivate HSV-1 infectivity.CV-N not only reduced the CPE of HSV-1 when added before or after viral infection,with a 50% inhibitory concentration (IC50) with 2.26 and 30.16μg/mL respectively,but it also decreased the copies of HSV-1 DNA in infected host cells.The encephalitis model for HSV-1 infection was conducted in Kunming mice,and treated with three dosages of CV-N (0.5,5 & 10 mg/kg) which was administered intraperitoneally at 2h,3d,5d,7d post infection.The duration for the appearance of symptoms of encephalitis and the survival days were recorded and brain tissue samples were obtained for pathological examination (HE staining).Compared with the untreated control group,in the 5mg/kg CV-N and 10mg/kg CV-N treated groups,the mice suffered light symptoms and the number of survival days were more than 9d and 14d respectively.HE staining also showed that in 5mg/kg CV-N and 10mg/kg CV-N treated groups,the brain cells did not show visible changes,except for a slight inflammation.Our results demonstrated that CV-N has pronounced antiviral activity against HSV-1 both in vitro and in vivo,and it would be a promising new candidate for anti-HSV therapeutics.
文摘Herpes simplex virus type-1 (HSV-1) is one of many pathogens that use the cell surface glycosaminoglycan heparan sulfate as a receptor. Heparan sulfate is highly expressed on the surface and extracellular matrix of virtually all cell types making it an ideal receptor. Heparan sulfate interacts with HSV-1 envelope glycoproteins gB and gC during the initial attachment step during HSV-1 entry. In addition,a modified form of heparan sulfate,known as 3-O-sulfated heparan sulfate,interacts with HSV-1 gD to induce fusion between the viral envelope and host cell membrane. The 3-O-sulfation of heparan sulfate is a rare modification which occurs during the biosynthesis of heparan sulfate that is carried out by a family of enzymes known as 3-O-sulfotransferases. Due to its involvement in multiple steps of the infection process,heparan sulfate has been a prime target for the development of agents to inhibit HSV entry. Understanding how heparan sulfate functions during HSV-1 infection may not only be critical for inhibiting infection by this virus,but it may also be crucial in the fight against many other pathogens as well.
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The Nation "863" Program of China(2006AA02A226)The Joint Funds of National Science Foundation of China (U0632010)+2 种基金The State KeyLaboratory of Phytochemistry and Plant Resources in West ChinaChinese Academy of Sciences (O807B11211, O807E21211)"211 grant of MOE"
文摘RNA interference (RNAi) is a process by which introduced small interfering RNA (siRNA) can cause the specific degradation of mRNA with identical sequences. The human herpes simplex virus type 1 (HSV-1) RR is composed of two distinct homodimeric subunits encoded by UL39 and UL40,respectively. In this study,we applied siRNAs targeting the UL39 and UL40 genes of HSV-1. We showed that synthetic siRNA silenced effectively and specifically UL39 and UL40 mRNA expression and inhibited HSV-1 replication. Our work offers new possibilities for RNAi as a genetic tool for inhibition of HSV-1 replication.
基金Supported by Natural Science Foundation of Jiangsu Province (No.BK20141346)Nanjing Science and Technology Development Plan (No.201402001)
文摘AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1(HSV-1) glycoprotein C(g C) and glycoprotein D(g D) will achieve better protective effect against herpes simplex keratitis(HSK) than DNA vaccine encoding gD alone. METHODS: DNA vaccine expressing gD or gC combined g D(g D.g C) were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293 T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2 wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS: Fusion protein g D.g C could be expressed successfully in cultured 293 T cells. And, p RSC-g C.g DIL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and s Ig A production, enhanced cytotoxicities of splenocytes and nature killer cells(NK),when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION: gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.
基金The National Natural Science Foundation of China (30670094, 30700028)the Ph.D. Programs Foundation of Ministry of Education of China (2006-0023008)
文摘Nuclear proteins often form punctiform structures, but the precise mechanism for this process is unknown. As a preliminary study, we investigated the aggregation of an HSV-1 immediate-early protein, infected-cell protein 22 (ICP22), in the nucleus by observing the localization of ICP22-EGFP fusion protein Results showed that, in high-level expression conditions, ICP22-EGFP gradually concentrates in the nucleus, persists throughout the cell cycle without disaggregation even in the cell division phase, and is finally distributed to daughter cells. We subsequently constructed a mammalian cell expression system, which had tetracycline- dependent transcriptional regulators. Consequently, the location of ICP22-EGFP in the nucleus changed with distinct induction conditions. This suggests that the cellular location of ICP22 is also influenced by promoter regulation, in addition to its own structure. Our findings provide new clues for the investigation of transcriptional regulation of viral genes. In addition, the non-protease reporter system we constructed could be utilized to evaluate the role of intemal ribosome entry sites (IRES) on transcriptional regulation.
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.
基金The National Natural Science Foundation of China (30670094)the Ph.D. Programs Foundation of Ministry of Education of China (20060023008)
文摘The protein HTRP (human transcription regulator protein) is encoded by the differential gene htrp and induced by Herpes simplex virus type 1 (HSV-1) infection in KMB-17 cells.HTRP was found to interact with SAP30 (mSin3A Association Protein),one of the components of co-repressor complex mSin3A,which is part of the deacetylation transfer enzyme HDAC.To reveal the biological significance of the interaction between HTRP and SAP30,real-time PCR and a dual-luciferase detecting system was used.The results indicate that HTRP could inhibit the transcription of a viral promoter,whose interaction with SAP30 synergistically affects transcriptional inhibition of the viral genes,and is related to HDAC enzyme activity.ChIP experiments demonstrate that HTRP could promote HDAC activity by increasing the deacetylation level of lysine 14 and lysine 9 in histone H3.
文摘Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive loss of cognitive functions in affected individuals. Brain tissue pathology is associated with the formation of senile plaques which result from the over-production of amyloid </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> (A</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">), due to the cleavage of a membrane bound glycoprotein. It is unclear what causes AD and its associated pathologies, but age and genetic predisposition play an import role in the likelihood of disease development. Studies have shown that the reactivation of latent herpes simplex virus 1 (HSV-1) infection can lead to the neuropathy of acute herpes simplex encephalitis (HSE), which causes similar symptoms to AD. HSV-1 infection is a known risk factor for the development of AD, but no study has determined a definitive causal relationship. Using the Qiagen In</span><span style="font-family:Verdana;">genuity Pathway Analysis (IPA) tool, the inhibitory relationship between therapeutic</span><span style="font-family:Verdana;">s for AD and HSV-1 were explored. Thirteen drugs developed to decrease A</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> buildup in AD and 32 drugs that act as HSV antivirals were retrieved from the data in the Qiagen Knowledge Base. These drugs were analyzed displayed as two separate networks. While many promising A</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> aggregation-targeting drugs have been discontinued due to lack of efficacy, HSV drugs could serve as potential therapeutics for those with AD. This review aims to describe new insights on how HSV-1 relates to the development of AD and highlight the mechanism of action of A</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-related drugs and HSV drugs in the context of AD. With HSV-1 being a likely candidate for the causation of AD, there is a need to study the effects of HSV antiviral drugs on those who have AD.