herpes
Characterization of human herpes virus 8 ORF59 protein (PF-8) and mapping of the processivity and viral DNA polymerase-interacting domains.

Chan SR, Chandran B.

Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160-7700, USA.

Human herpes virus 8 (HHV-8) or Kaposi's sarcoma-associated herpes virus (KSHV) ORF59 protein (PF-8) is a processivity factor for HHV-8 DNA polymerase (Pol-8) and is homologous to processivity factors expressed by other herpes viruses, such as herpes simplex virus type 1 UL42 and Epstein-Barr virus BMRF1. The interaction of UL42 and BMRF1 with their corresponding DNA polymerases is essential for viral DNA replication and the subsequent production of infectious virus. Using HHV-8-specific monoclonal antibody 11D1, we have previously identified the cDNA encoding PF-8 and showed that it is an early-late gene product localized to HHV-8-infected cell nuclei (S. R. Chan, C. Bloomer, and B. Chandran, Virology 240:118-126, 1998). Here, we have further characterized PF-8. This viral protein was phosphorylated both in vitro and in vivo. PF-8 bound double-stranded DNA (dsDNA) and single-stranded DNA independent of DNA sequence; however, the affinity for dsDNA was approximately fivefold higher. In coimmunoprecipitation reactions, PF-8 also interacted with Pol-8. In in vitro processivity assays with excess poly(dA):oligo(dT) as a template, PF-8 stimulated the production of elongated DNA products by Pol-8 in a dose-dependent manner. Functional domains of PF-8 were determined using PF-8 truncation mutants. The carboxyl-terminal 95 amino acids (aa) of PF-8 were dispensable for all three functions of PF-8: enhancing processivity of Pol-8, binding dsDNA, and binding Pol-8. Residues 10 to 27 and 279 to 301 were identified as regions critical for the processivity function of PF-8. Interestingly, aa 10 to 27 were also essential for binding Pol-8, whereas aa 1 to 62 and aa 279 to 301 were involved in binding dsDNA, suggesting that the processivity function of PF-8 is correlated with both the Pol-8-binding and the dsDNA-binding activities of PF-8.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069986&dopt=Abstract herpes medicine



herpes
Amino acid substitutions in the V domain of nectin-1 (HveC) that impair entry activity for herpes simplex virus types 1 and 2 but not for Pseudorabies virus or bovine herpes virus 1.

Martinez WM, Spear PG.

Department of Microbiology-Immunology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.

The entry of herpes simplex virus (HSV) into cells requires the interaction of viral glycoprotein D (gD) with a cellular gD receptor to trigger the fusion of viral and cellular membranes. Nectin-1, a member of the immunoglobulin superfamily, can serve as a gD receptor for HSV types 1 and 2 (HSV-1 and HSV-2, respectively) as well as for the animal herpes viruses porcine pseudorabies virus (PRV) and bovine herpes virus 1 (BHV-1). The HSV-1 gD binding domain of nectin-1 is hypothesized to overlap amino acids 64 to 104 of the N-terminal variable domain-like immunoglobulin domain. Moreover, the HSV-1 and PRV gDs compete for binding to nectin-1. Here we report that two amino acids within this region, at positions 77 and 85, are critical for HSV-1 and HSV-2 entry but not for the entry of PRV or BHV-1. Replacement of either amino acid 77 or amino acid 85 reduced HSV-1 and HSV-2 gD binding but had a lesser effect on HSV entry activity, suggesting that weak interactions between gD and nectin-1 are sufficient to trigger the mechanism of HSV entry. Substitution of both amino acid 77 and amino acid 85 in nectin-1 significantly impaired entry activity for HSV-1 and HSV-2 and eliminated binding to soluble forms of HSV-1 and HSV-2 gDs but did not impair the entry of PRV and BHV-1. Thus, amino acids 77 and 85 of nectin-1 form part of the interface with HSV gD or influence the conformation of that interface. Moreover, the binding sites for HSV and PRV or BHV-1 gDs on nectin-1 may overlap but are not identical.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12072525&dopt=Abstract herpes medicine



herpes
Striking similarity of murine nectin-1alpha to human nectin-1alpha (HveC) in sequence and activity as a glycoprotein D receptor for alphaherpes virus entry.

Shukla D, Dal Canto MC, Rowe CL, Spear PG.

Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.

A cDNA encoding the murine homolog of human nectin-1alpha (also known as poliovirus receptor-related protein 1 [Prr1] and herpes virus entry protein C [HveC]) was isolated. The protein encoded by this cDNA proved to be 95% identical in sequence to the human protein and to have similar herpes virus entry activity. Upon expression of the murine cDNA in hamster cells resistant to alphaherpes virus entry, the cells became susceptible to the entry of herpes simplex virus types 1 and 2 (HSV-1 and -2), pseudorabies virus, and bovine herpes virus 1. HSV envelope glycoprotein D (gD), a viral ligand for human nectin-1alpha, is also a ligand for the murine homolog based on evidence that (i) a soluble hybrid protein composed in part of the murine nectin-1 ectodomain bound specifically to purified soluble forms of HSV-1 and HSV-2 gD as demonstrated by enzyme-linked immunosorbent assay, (ii) a soluble hybrid of HSV-1 gD bound to hamster cells expressing murine nectin-1alpha but not to control cells, and (iii) cells expressing both murine nectin-1alpha and one of the alphaherpes virus gDs were resistant to entry of HSV-1, indicative of interference with entry resulting from interactions of cell-associated gD with the entry receptor. Northern blot analysis revealed that nectin-1 is expressed in most of the mouse tissues examined and at high levels in the brain, skin, and kidneys. Immunocytochemical localization demonstrated the presence of nectin-1 in epithelial cells of the mouse vagina and also in neuronal cells of the central nervous system, suggesting an expression pattern relevant to both infection at a portal of entry and spread of infection to the brain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11090177&dopt=Abstract herpes medicine



herpes
Public Health Strategies to Prevent Genital Herpes: Where Do We Stand?

Handsfield HH.

Harborview Medical Center, Box 359777, 325 Ninth Avenue, Seattle, WA 98104-2499, USA. hhh u.washington.edu.

At least 25% of the United States population has overt or subclinical genital herpes simplex virus (HSV) infection, and herpes probably is the sexually transmitted disease of greatest concern to sexually active persons, aside from AIDS. In addition to its direct clinical and psychosexual complications, genital herpes is an important determinant of sexual transmission of HIV. Genital herpes is usually transmitted by persons with subclinical infection, whether entirely asymptomatic or with unrecognized symptoms. Although the composition and efficacy of a national genital herpes prevention program are in debate, clinicians should adopt a public health perspective in managing patients to help prevent transmission. Specific approaches include accurate diagnosis of genital ulcer disease by routine use of virologic tests for HSV; use of type-specific serologic tests to diagnose subclinical HSV infection in patients' sex partners and others at high risk; counseling patients to recognize symptoms and defer sex with uninfected partners when symptomatic; and serologic testing and counseling of pregnant women and their partners to prevent neonatal herpes. Antiviral chemotherapy may be effective in preventing herpes-related cesarean sections, and its efficacy in preventing sexual transmission of HSV is under study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11095834&dopt=Abstract herpes medicine



herpes
[Reactivation of herpes virus infections by vaccination: evidence or coincidence?]

[Article in German]

Walter R, Hartmann K, Pool V, Gargiullo P, Kuhn M.

Departement fur Innere Medizin, Universitatsspital Zurich.

Varicella zoster and herpes simplex viruses cause latent infections by persisting in human cells. Reactivation has been associated with increasing age, immunosuppression, cancer, stress, fever, exposure to ultraviolet light, and tissue damage. Based on three cases reported to the Swiss Drug Monitoring Centre SANZ, we postulated previously that vaccinations may trigger reactivation of herpes virus infections due to vaccine-induced immunomodulation. In the meantime, 10 new cases of reactivated herpes virus infections soon after vaccinations have been reported. They involved 5 women and 5 men with an age range between 16 and 60. In only one case had a trauma preceded, otherwise healthy subjects with no known relevant comorbidity were vaccinated. The clustering of reports after publication points to a previous underreporting of similar cases. This may be explained by the fact that both vaccinations and reactivations of herpes virus infections are frequent, and a causal link is not suspected. However, these new cases do not prove causality, and extensive epidemiological or experimental studies are needed to elucidate the possible link between vaccination and reactivation of herpes virus infections.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11103441&dopt=Abstract herpes medicine



herpes
Herpesvirus saimiri pathogenicity enhanced by thymidine kinase of herpes simplex virus.

Hiller C, Tamguney G, Stolte N, Matz-Rensing K, Lorenzen D, Hor S, Thurau M, Wittmann S, Slavin S, Fickenscher H.

Institut fur Klinische und Molekulare Virologie, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Schlossgarten 4, Erlangen, D-91054, Germany.

Herpesvirus saimiri can be used as an efficient gene expression vector for human T lymphocytes and thus may allow applications in experimental leukemia therapy. We constructed recombinant viruses for the functional expression of the thymidine kinase (TK) of herpes simplex virus type 1 (HSV) as a suicide gene. These viruses reliably allowed the targeted elimination of transduced nonpermissive human T cells in vitro after the administration of ganciclovir. To test the reliability of this function under the most stringent permissive conditions, in this study we analyzed the influence of the prodrugs ganciclovir and acyclovir in common marmosets on the acute leukemogenesis induced by either wild-type herpes virus saimiri C488 or by a recombinant derivative expressing TK of HSV. Antiviral drug treatment did not influence the rapid development of acute disease. In contrast, the presence of the HSV tk gene resulted in a faster disease progression. In addition, HSV TK-expressing viruses showed faster replication than wild-type virus in culture at low serum concentrations. Thus, HSV TK accelerates the replication of herpes virus saimiri and enhances its pathogenicity. This should be generally considered when HSV TK is applied as a transgene in replication-competent DNA virus vectors for gene therapy. Copyright 2000 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11118367&dopt=Abstract herpes medicine



herpes
The genome of turkey herpes virus.

Afonso CL, Tulman ER, Lu Z, Zsak L, Rock DL, Kutish GF.

Plum Island Animal Disease Center, Agricultural Research Service, U. S. Department of Agriculture, Greenport, New York 11944, USA.

Here we present the first complete genomic sequence of Marek's disease virus serotype 3 (MDV3), also known as turkey herpes virus (HVT). The 159,160-bp genome encodes an estimated 99 putative proteins and resembles alphaherpes viruses in genomic organization and gene content. HVT is very similar to MDV1 and MDV2 within the unique long (UL) and unique short (US) genomic regions, where homologous genes share a high degree of colinearity and their proteins share a high level of amino acid identity. Within the UL region, HVT contains 57 genes with homologues found in herpes simplex virus type 1 (HSV-1), six genes with homologues found only in MDV, and two genes (HVT068 and HVT070 genes) which are unique to HVT. The HVT US region is 2.2 kb shorter than that of MDV1 (Md5 strain) due to the absence of an MDV093 (SORF4) homologue and to differences at the UL/short repeat (RS) boundary. HVT lacks a homologue of MDV087, a protein encoded at the UL/RS boundary of MDV1 (Md5), and it contains two homologues of MDV096 (glycoprotein E) in the RS. HVT RS are 1,039 bp longer than those in MDV1, and with the exception of an ICP4 gene homologue, the gene content is different from that of MDV1. Six unique genes, including a homologue of the antiapoptotic gene Bcl-2, are found in the RS. This is the first reported Bcl-2 homologue in an alphaherpes virus. HVT long repeats (RL) are 7,407 bp shorter than those in MDV1 and do not contain homologues of MDV1 genes with functions involving virulence, oncogenicity, and immune evasion. HVT lacks homologues of MDV1 oncoprotein MEQ, CxC chemokine, oncogenicity-associated phosphoprotein pp24, and conserved domains of phosphoprotein pp38. These significant genomic differences in and adjacent to RS and RL regions likely account for the differences in host range, virulence, and oncogenicity between nonpathogenic HVT and highly pathogenic MDV1.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11134310&dopt=Abstract herpes medicine



herpes
Herpesviruses in HIV-periodontitis.

Contreras A, Mardirossian A, Slots J.

Department of Periodontology, School of Dentistry, University of Southern California, Los Angeles 90089-0641, USA.

BACKGROUND/AIMS: Human herpes virus-associated diseases exhibit elevated morbidity and mortality in patients infected with human immunodeficiency virus (HIV).This study aimed to investigate the occurrence of herpes viruses in HIV-periodontitis. METHOD: Gingival biopsies from periodontitis lesions of 21 HIV-patients and 14 non HIV-patients were studied. Nested-polymerase chain reaction methods were employed to detect human cytomegalovirus, Epstein-Barr virus type 1 and 2 (EBV-1, EBV-2), herpes simplex virus, human herpes virus (HHV)-6, HHV-7 and HHV-8. RESULTS: Gingival biopsies from HIV-periodontitis lesions showed on average 4.0 herpes virus species and gingival biopsies from HIV periodontitis lesions of non-HIV patients revealed an average of 1.9 herpes virus species (p<0.001). Occurrence of 4 to 6 different herpes viruses was more common in HIV- than in non HIV-gingival biopsies (71% vs. 7%) (p<0.001). EVB-2 was detected in 12 (57%) biopsies from HIV-periodontitis but was absent in non HIV-periodontitis biopsies (p= 0.002). HHV-6 also occurred in significantly higher frequency in HIV-periodontitis (71%) than in non HIV-periodontitis (21%) (p=0.01). HHV-8 was detected only in biopsies from HIV-periodontitis lesions.. CONCLUSION: HIV-periodontitis seems to be associated with elevated occurrence of EBV-2, HHV-6 and herpes virus co-infections compared to periodontitis in non-HIV-patients. The periodontopathic significance of herpes viruses in HIV-periodontitis constitutes a research topic of considerable interest.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11142675&dopt=Abstract herpes medicine