Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells

Receptors for the Fc portion of immunoglobulins or for the third component of complement (C3) are present on a variety of circulating and fixed tissue cells including granulocytes, monocytes, lymphocytes and glomerular epithelial cells. Cells which lack Fc receptors may express them after infection by herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus or varicella zoster virus. We recently reported that infection by HSV-1 induces both Fc and C3 receptors on human endothelial cells. Glycoprotein E of HSV-1 has been shown to function as an Fc receptor. We now demonstrate that glycoprotein C (gC) of HSV-1 functions as a C3b receptor. This receptor appears following HSV-1, but not HSV-2, infection. Detection of the C3b receptor is blocked by monoclonal antibodies to glycoprotein C (gC) of HSV-1, but not by monoclonal antibodies to other HSV-1 glycoproteins. In addition, the MP mutant of HSV-1, which lacks gC, fails to express a C3b receptor. These results assign a new function of gC of HSV-1 and demonstrate potentially important differences between HSV-1 and HSV-2 glycoproteins.     

Varicella-zoster virus DNA in human sensory ganglia

Varicella-zoster virus (VZV) causes chickenpox and shingles. Clinical and epidemiological evidence indicates that following an episode of childhood chickenpox (varicella), VZV becomes latent, presumably in dorsal root ganglia, and is reactivated many years later to produce shingles (zoster) in adults. VZV has been demonstrated in ganglia by electron microscopy and by indirect immunofluorescence, and infectious viral particles have been isolated from acutely infected ganglia of patients who died of disseminated VZV infection. However, VZV has not been detected in the ganglia of humans without recent exposure to VZV. Tissue culture explant methods that have been successful in the isolation of herpes simplex virus from ganglia have so far failed in the isolation or reactivation of VZV from trigeminal and other dorsal root ganglia. We describe here the detection of VZV DNA sequences in an acutely infected human sacral ganglion and in normal trigeminal ganglia. These findings support the hypothesis that VZV is latent in normal human ganglia.     

Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype

Recent advances in molecular genetics have led to the possibility of using large DNA viruses, such as vaccinia virus, as a biological delivery system for immunizing man against unrelated disease-causing agents. When live vaccinia virus recombinants expressing the hepatitis B virus surface antigen (HBsAg), the influenza A virus haemagglutinin, the herpes simplex virus (HSV) type 1 D glycoprotein, the rabies virus G glycoprotein and the vesicular stomatitis virus G glycoprotein were used for immunization, animals were protected upon challenge with the appropriate pathogenic agent. A major concern with using such vaccines, however, stems from the previously documented vaccinia virus-associated post-immunizing complications. We present here experimental evidence that thymidine kinase-negative (TK-) vaccinia virus recombinants, constructed by inserting a variety of DNA coding sequences into the vaccinia virus tk gene, are less pathogenic for mice than wild-type virus.     

Antiviral activities of extracts from Hong Kong seaweeds

We extracted six Hong Kong brown seaweed species with hot water for their antiviral properties. The cytotoxicity and antiviral activity of these extracts were tested by MTT [3-（4,5-dimethylthiazol-2-yl）-2,5-diphenlytetrezolium bromide] method, cytopathic effect reduction assay, and plaque reduction assay. The antiviral effect was further determined by flow cytometric analysis. The results showed that most of these extracts inhibited the propagation of herpes simplex virus types 1 and 2 （HSV-1 and HSV-2） standard strains with very low cytotoxicity to the host cells. The extracts ofHydroclathrus clathratus and Lobophora variegata showed more potential anti-HSV activities than the extracts of the other four seaweeds. They also had moderate antirespiratory syncytial virus （RSV） activities but could not inhibit influenza A virus. Hydroclathrus clathratus was further extracted by diluted acid and alkali and the antiviral effects of the extracts were also detected. The result showed that the hot water extract contained the main carbohydrate components that exhibited the antiviral activities against various strains of HSV, including the acyclovir-resistant strain. HI-3, a compound fractionated from this hot water extract, showed a dose-dependent anti-HSV activity in flow cytometric analysis and plaque reduction assay.     

Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance

Acyclovir (9-[2-hydroxyethoxymethyl]guanine or ACV) is a nucleoside analogue with considerable potential for the treatment of herpes simplex virus (HSV) infections in man. Two virus-coded enzymes are important in the mechanism of action of this drug: thymidine kinase (TK) which initiates its activation by converting it to the monophosphate and DNA polymerase whose action is inhibited by ACV triphosphate. Changes in either gene may confer resistance, but all reported mutations in the TK gene have resulted in failure of the resistant virus to induce appreciable levels of the enzyme. Such TK- mutants arise readily in tissue culture systems where the enzyme is non-essential for virus replication, but in animals they show considerably reduced pathogenicity and neurovirulence. We now describe the isolation of a resistant mutant which induces a TK of altered substrate specificity and we show that this virus retains pathogenicity for mice with only a slight attenuation of neurovirulence.     

紫球藻及其多糖的研究

就近年来紫球藻生理活性物质中的硫酸酯多糖的研究进展作一综述．紫球藻多糖具有抗病毒、抑制病毒复制,对单疱疹病毒1型和2型(HSV1,2)及水痘一带状疱疹病毒(VZV)明显的抗性,并可抑制小鼠癌细胞的发展。     

HIV susceptibility conferred to human fibroblasts by cytomegalovirus-induced Fc receptor

The main receptor for the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) on T and B lymphocytes, monocytes and macrophages is the CD4 antigen 1-3. Infection of these cells is blocked by monoclonal antibodies to CD4(1,2) and by recombinant soluble CD4(4-9). Expression of transfected CD4 on the surface of HeLa and other human cells renders them susceptible to HIV infection 10. HIV-antibody complexes can also infect monocytes and macrophages by means of receptors for the Fc portion of immunoglobulins (FcR)11-13), or complement receptors 14,15. The expression of IgG FcRs can be induced in cells infected with human herpes viruses such as herpes simplex virus type 1 (HSV-1)16,17 and human cytomegalovirus (CMV)18-21. Here we demonstrate that FcRs induced by CMV allow immune complexes of HIV to infect fibroblasts otherwise not permissive to HIV infection. Infection was inhibited by prior incubation with human IgG, but not by anti-CD4 antibody or by recombinant soluble CD4. Once HIV had entered CMV-infected cells by means of the FcR, its replication could be enhanced by CMV transactivating factors. Synergism between HIV and herpes viruses could also operate in vivo, enhancing immunosuppression and permitting the spread of HIV to cells not expressing CD4.     

噻唑烷-4-酮衍生物抗HCMV和VZV的活性

利用病毒噬斑抑制法,探讨了2,3-二芳基-1,3-噻唑烷-4-酮(化合物1和2)、含糖基的1,3-噻唑烷-4-酮(化合物3和4)抗人巨细胞疱疹病毒(HCMV)和水痘带状疱疹病毒(VZV)活性.结果表明:2,3-二芳基-1,3-噻唑烷-4-酮是一类新型高效的抗HCMV化合物,而含糖基的1,3-噻唑烷-4-酮可能是一类比较...     

Specific inhibition of herpesvirus ribonucleotide reductase by synthetic peptides

Ribonucleotide reductase is an essential enzyme for DNA synthesis in all prokaryotic and eukaryotic cells; it catalyses the reductive conversion of ribonucleotides to deoxyribonucleotides. Several herpesviruses including herpes simplex virus type 1 (HSV-1), HSV-2, pseudorabies virus (PRV), equine herpesvirus type 1 (EHV-1) and Epstein-Barr virus (EBV) have been found to induce novel ribonucleotide reductase activities. There is evidence that the HSV-1 ribonucleotide reductase activity is virus-encoded and essential for virus replication. This makes herpesvirus ribonucleotide reductases potential targets for antiviral chemotherapy. The HSV-1-encoded enzyme consists of two subunits: V136, the large subunit of relative molecular mass (Mr) 136,000 (136K) (RR1), which has been shown to be essential for enzyme activity, and V38, the small subunit (RR2) which forms a complex with the large subunit and is also likely to be essential for enzyme activity. Two particular features of the enzyme make it an attractive antiviral target. First, there is evidence for a common, highly conserved herpesvirus ribonucleotide reductase and second, the interaction between the large and small subunits may itself be exploitable. Here we identify a synthetic peptide which specifically inhibits the activity of virus-induced enzyme. We deduce that the mechanism of inhibition involves interference with the normal interaction between the two types of subunit.     

Genetic retrieval of viral genome sequences from herpes simplex virus transformed cells

Oncogenic transformation of cultured cells by inactivated herpes simplex virus (HSV) types 1 and 2 has been demonstrated. Expression of HSV information in these transformed cells has been shown by immunofluorescence studies, detection of HSV neutralizing antibody in sera from tumour-bearing animals and by hybridization of HSV-specific RNA. Molecular hybridization studies of DNA from HSV-2 transformed hamster cells have detected up to 40% of the HSV genome present in several copies. Complementation of three HSV-2 temperature-sensitive mutants when superinfecting the RE1 rat embryo cell line (transformed by the HSV-2 temperature-sensitive mutant ts1) suggests that resident viral genes can be expressed. Brown et al. used a similar approach to detect HSV information latent in human ganglia. We report here retrieval of intertypic HSV recombinants from HSV transformed cells after superinfection with ts mutants of the alternative serotype of HSV. Restriction enzyme analysis which clearly differentiates between HSV-1 and HSV-2 DNA has demonstrated the isolation of recombinants spanning the genome and of virus indistinguishable from the original transforming virus.     

Is ribonucleotide reductase the transforming function of herpes simplex virus 2?

Transformation of cells by herpes simplex virus 2 (HSV-2) can be induced by the BglII C (0.43-0.58 map units) or N (0.58-0.625) fragments of the viral genome. Sequences partially overlapping both fragments (0.566-0.602) encode two 3' coterminal mRNAs; these in turn direct the synthesis of two related polypeptides of molecular weight 140,000 (140K) and 35K (refs 4, 7), which may be involved in transformation. Recently, a temperature-sensitive (ts) mutation affecting HSV-induced ribonucleotide reductase has been mapped within this common region (B.M. Dutia, personal communication). We have partially purified the induced reductase and raised a rabbit antiserum to it which inhibits the enzyme activity and immunoprecipitates from infected cells a 144K polypeptide and minor species including a 38K polypeptide. Here we show that a monoclonal antibody to the putative transforming proteins competes with the rabbit serum for the 144K and 38K antigens and also immunoprecipitates specifically the induced reductase activity. These results suggest a possible role for ribonucleotide reductase in HSV-2-induced transformation.     

应用PCR技术检测单纯疱疹病毒

采用聚合酶链反应（ＰＣＲ）技术，检测２０５例样本，其中单纯疱疹病毒阳性６５例，阳性率３１．７％．ＰＣＲ技术具有高度的敏感性和特异性，为疱疹病毒感染的临床早期准确诊断、判定药物疗效和流行病学研究等提供了有效的手段     

利多卡因凝胶治疗带状疱疹后神经痛临床疗效分析

目的探讨利多卡因凝胶治疗带状疱疹后神经痛的临床疗效.方法随机将86例带状疱疹后神经痛患者分为两组,对照组43例使用双氯芬酸凝胶治疗,治疗组43例使用利多卡因凝胶治疗,观察比较两组临床疗效.结果观察组治疗总有效率(93.02%)显著优于对照组(76.74%)(P0.05);治疗前,两组患者VAS评分无统计学意义(P0.05);治疗后1,2,4周观察组VAS评分(13.5±14.2),(18.5±17.1),(20.8±19.0)分,均显著优于对照组(6.8±12.5),(7.3±12.4),(8.2±14.3)分,差异具有统计学意义(P0.05).结论利多卡因凝胶治疗带状疱疹后神经痛,效果明显,值得进一步深入研究与临床推广使用.     

Glycyrrhizic acid inhibits virus growth and inactivates virus particles.

Screening investigations in antiviral action of plant extracts have revealed that a component of Glycyrrhiza glabra roots, found to be glycyrrhizie acid, is active against viruses. We report here that this drug inhibits growth and cytopathology of several unrelated DNA and RNA viruses, while not affecting cell activity and ability to replicate. In addition, glycyrrhizic acid inactivates herpes simplex virus particles irreversibly.     

Xyloadenosine analogue of (A2'p)2A inhibits replication of herpes simplex viruses 1 and 2

Molecules of the structure ppp(A2'p)2A containing a 2' leads to 5' phosphodiester bond, commonly abbreviated as 2-5A, are synthesized in interferon-treated virally-infected cells and have been implicated in several systems as contributing to interferon's antiviral activity. The 2-5A binds to and subsequently activates an endogenous endonuclease, ultimately resulting in degradation of RNA. We have been interested in the use of 2-5A analogues to achieve antiviral activity without the use of interferon. For this approach to be successful, analogues must be synthesized with an increased stability (native 2-5A is rapidly degraded by cellular phosphodiesterases) and with increased ability to enter intact cells. Removal of the highly-negative charged 5' terminal phosphates from ppp(A2'p)2A results in formation of the 'core' species, (A2'p)2A, which should be able to penetrate intact cells more readily. While Kimchi et al. have shown that 2-5A core has an antimitogenic effect in mouse spleen lymphocytes and 3T3 fibroblasts, Williams and Kerr have reported lack of antiviral activity against Semliki Forest virus or encephalomyocarditis virus by exogenously-administered 2-5A core. We have previously determined that (xyloA2'p)2xyloA (abbreviated as xylo 2-5A core), the xyloadenosine analogue of the 5'-terminally dephosphorylated 2-5A core, is over 100 times more stable than the parent 2-5A core species. We now report that this xylo 2-5A core inhibits replication of herpes simplex viruses 1 and 2 in vitro, with greater than 100 times the activity of the parent 2-5A core. The mechanism of antiviral action of the 2-5A core analogue appears to involve a pathway different from that activated by the parent 5' triphosphorylated 2-5A species.     

The oncogenic potential of herpes simplex viruses: evidence for a 'hit-and-run' mechanism

Experiments to determine the mechanism of transformation of herpes simplex virus (HSV) have identified fragments of viral DNA which are able to initiate transformation. No set of viral genes seems to be consistently retained or expressed in the transformed cells or in human cervical tumours, suggesting that viral DNA is not needed to maintain the transformed phenotype. In fact there is no conclusive evidence that initiation of neoplasia is mediated by a viral protein. Here we revisit the 'hit-and-run' hypothesis and its implications for HSV-induced tumorigenicity.