herpes
Herpesviruses in periodontal pocket and gingival tissue specimens.

Contreras A, Nowzari H, Slots J.

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

Human cytomegalovirus (HCMV) and Epstein-Barr virus type 1 (EBV-1) are frequently detected in crevicular fluid of deep periodontal pockets, but little or no information is available on occurrence of herpes viruses in gingival tissue. This investigation studied the presence of herpes viruses in periodontal pockets and the corresponding gingival tissues from 11 periodontally healthy and 14 periodontitis sites. A nested-polymerase chain reaction was employed to identify the presence of HCMV, EBV-1, EBV-2, herpes simplex virus, human herpes virus (HHV)-6, HHV-7 and HHV-8 in each test sample. In healthy periodontal sites, HCMV was detected in 1 (9%) and EBV-1 in 2 (18%) pocket samples, and HCMV was detected in 2 (18%) and EBV-1 in 3 (27%) gingival tissue samples. In periodontitis lesions, HCMV was detected in 9 (64%) pocket samples and in 12 (86%) gingival tissue samples, and EBV-1 was detected in 6 (43%) pocket samples and in 11 (79%) gingival tissue samples. HHV-6 and HHV-8 were detected exclusively in gingival tissue samples. The present findings confirm the frequent presence of HCMV and EBV-1 in periodontitis lesions and suggest using gingival tissue specimens for detecting periodontal HHV-6, HHV-7 and HHV-8.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11155159&dopt=Abstract herpes medicine



herpes
Glycoprotein D homologs in herpes simplex virus type 1, pseudorabies virus, and bovine herpes virus type 1 bind directly to human HveC(nectin-1) with different affinities.

Connolly SA, Whitbeck JJ, Rux AH, Krummenacher C, van Drunen Littel-van den Hurk S, Cohen GH, Eisenberg RJ.

Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104, USA. sconnoll mail.med.upenn.edu

Distinct subsets of human receptors for alphaherpes viruses mediate the entry of herpes simplex virus (HSV), pseudorabies virus (PrV), or bovine herpes virus type 1 (BHV-1) into cells. Glycoprotein D (gD) is essential for receptor-mediated entry of all three viruses into cells. However, the gD homologs of these viruses share only 22-33% amino acid identity. Several entry receptors for HSV have been identified. Two of these, HveA (HVEM) and HveC (nectin-1), mediate entry of most HSV-1 and HSV-2 strains and are bound directly by HSV gD. A third receptor, HveB (nectin-2), mediates entry of HSV-2 and only a limited number of HSV-1 strains. HveB and HveC can also serve as entry receptors for PrV, whereas only HveC can serve this function for BHV-1. We show here that gD from PrV and BHV-1 binds directly to the human receptors that mediate PrV and BHV-1 entry. We expressed soluble forms of PrV gD and BHV-1 gD using recombinant baculoviruses and purified each protein. Using ELISA, we detected direct binding of PrV gD to HveB and HveC and direct binding of BHV-1 gD to HveC. Biosensor analysis revealed that PrV gD had a 10-fold higher affinity than HSV-1 gD for human HveC. In contrast, the binding of BHV-1 gD to HveC was weak. PrV gD and HSV-1 gD competed for binding to the V domain of HveC and both inhibited entry of the homologous and heterologous viruses. These data suggest that the two forms of gD bind to a common region on human HveC despite their low amino acid similarity. Based on affinities for human HveC, we predict a porcine HveC homolog may be important for PrV infection in its natural host, whereas a BHV-1 infection in its natural host may be mediated by a receptor other than a bovine HveC homolog. Copyright 2001 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11162814&dopt=Abstract herpes medicine



herpes
Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus.

Zaal MJ, Volker-Dieben HJ, Wienesen M, D'Amaro J, Kijlstra A.

Department of Ophthalmology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. mjw.zaal azu.nl

PURPOSE: Longitudinal analysis of varicella-zoster virus DNA on the ocular surface of patients with herpes zoster ophthalmicus. METHODS: Clinical specimens were obtained from the bulbar conjunctival surface with a cotton-tipped swab at weekly intervals for 6 consecutive weeks from 21 patients with acute ophthalmic zoster with a skin rash duration of less than 7 days. All patients received oral valacyclovir 1000 mg three times daily for 10 days without additional corticosteroids. The swabs were analyzed by means of polymerase chain reaction for the presence of varicella-zoster virus and herpes simplex virus type 1 DNA. Conjunctival swabs were also obtained from a control group of 20 patients with cataract. RESULTS: On inclusion, varicella-zoster virus DNA was present on the ocular surface of 19 of the 21 patients. Six varicella-zoster virus DNA-positive patients had no signs of ocular inflammation. All control swabs were negative for both varicella-zoster virus and herpes simplex virus DNA. The duration of varicella-zoster virus DNA detection from rash onset varied from 2 to 34 days. The number of days between the onset of herpes zoster skin rash and the latest positive varicella-zoster virus DNA test was significantly longer in patients whose age was equal to or above the median age of 66 years than in the younger patients (Mann-Whitney test: P =.0004). At 6-week follow-up, all conjunctival swabs were negative for varicella-zoster virus DNA. However, at that time, the eyes of seven patients were still inflamed. CONCLUSION: The duration of varicella-zoster virus DNA shedding in herpes zoster ophthalmicus is highly variable and age dependent, and is probably related to the host immune response.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11162975&dopt=Abstract herpes medicine



herpes
Rapid acquisition of entire DNA polymerase gene of a novel herpes virus from green turtle fibropapilloma by a genomic walking technique.

Yu Q, Hu N, Lu Y, Nerurkar VR, Yanagihara R.

Retrovirology Research Laboratory, Pacific Biomedical Research Center, University of Hawaii at Manoa, Honolulu, HI 96816, USA. yu pbrc.hawaii.edu

A 4837-bp sequence of a newfound green turtle herpes virus (GTHV), implicated in the etiology of green turtle fibropapilloma, was obtained from tumor tissues of a green turtle with fibropapilloma using a genomic walking method based on restriction enzyme digestion, self-ligation and inverse polymerase chain reaction (IPCR). The 4837-bp sequence was 56.23% G/C rich and contained three nonoverlapping open reading frames (ORF). The largest ORF (3507-bp) encoded the DNA polymerase gene (pol gene), which exhibited a high degree of homology at both amino acid and nucleotide levels with the DNA pol genes of human and animal herpes viruses, with a predicted protein of 1169 amino acids and molecular weight of 132.6 kilodaltons. The ATG at 518 to 520 was the first initiation codon in the ORF and was presumed to be the first methionine codon of the pol gene. Phylogenetic analysis, based on the amino acid sequence of the GTHV DNA pol gene and the corresponding regions of other known human and animal herpes viruses, indicated that GTHV belonged to the Alphaherpesvirinae subfamily. The upstream ORF of the pol gene encoded the N-terminal region of the GTHV homologue of the DNA-binding protein gene, whereas the downstream ORF was the C-terminal region of a gene which was homologous to ORFs conserved in human and animal herpes viruses, i.e., herpes simplex virus 1 (HSV1) gene UL31, Epstein-Barr virus (EBV) gene BFLF2, equine herpes virus 1 (EHV1) gene 29, and alcelaphine herpes virus 1 (AHV1) hypothetical protein 69 gene. The arrangement of these three genes in GTHV genome was identical to that seen in other alphaherpes viruses. The sequence and location of the DNA pol gene in the GTHV genome should greatly facilitate future studies of the viral life cycle.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11164500&dopt=Abstract herpes medicine



herpes
Interaction of HSV-1 infected peripheral blood mononuclear cells with cultured dermal microvascular endothelial cells: a potential model for the pathogenesis of HSV-1 induced erythema multiforme.

Larcher C, Gasser A, Hattmannstorfer R, Obexer P, Furhapter C, Fritsch P, Sepp N.

Institute of Hygiene, University of Innsbruck, Innsbruck, Austria.

The effect of herpes virus infection on human dermal microvascular endothelial cells and herpes-virus-1-infected peripheral blood mononuclear cells on human dermal microvascular endothelial cells was studied as a model of herpes-associated erythema multiforme. After infection of human dermal microvascular endothelial cells with native herpes virus and overnight culture, 60%--90% of human dermal microvascular endothelial cells showed cytopathic effects. HLA class I molecules and CD31 (PECAM-1) surface expression in herpes-virus-infected endothelial cells were substantially downregulated, whereas CD54 (ICAM-1) remained unchanged. Cocultivation with herpes-virus-1-infected peripheral blood mononuclear cells left characteristic plaques on the human dermal microvascular endothelial cell monolayer; however, very few human dermal microvascular endothelial cells (1%--3%) were infected. Adhesion molecule expression of human dermal microvascular endothelial cells cocultivated with herpes-virus-infected peripheral blood mononuclear cells demonstrated a 5-fold increase in CD54 expression, a 2-fold increase in HLA class I expression, but no change of CD31 by fluorescence-activated cell sorter analysis. Incubation of human dermal microvascular endothelial cells with ultraviolet-C irradiated herpes-virus-infected peripheral blood mononuclear cells had no effect on morphology or adhesion molecule expression levels. Changes of adhesion molecule expression by direct infection or cocultivation with peripheral blood mononuclear cells (with native and ultraviolet-C inactivated herpes virus infection) were also documented at the mRNA level. Adhesion assays demonstrated an increased binding of herpes-virus-infected peripheral blood mononuclear cells versus noninfected peripheral blood mononuclear cells to noninfected human dermal microvascular endothelial cells. Our results suggest that incubation of herpes-virus-infected peripheral blood mononuclear cells with human dermal microvascular endothelial cells induces significant upregulation of CD54 and major histocompatibility complex class I molecules in the surrounding noninfected human dermal microvascular endothelial cells, which is associated with an increased binding of peripheral blood mononuclear cells. Our in vitro findings may serve as a model for herpes-associated erythema multiforme possibly explaining the dermal inflammatory reaction seen in that condition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11168811&dopt=Abstract herpes medicine



herpes
Herpes simplex virus type 2 seroepidemiology in Spain: prevalence and seroconversion rate among sexually transmitted disease clinic attendees.

Varela JA, Garcia-Corbeira P, Aguanell MV, Boceta R, Ballesteros J, Aguilar L, Vazquez-Valdes F, Dal-re R.

Gijon STD Clinic, Spain.

BACKGROUND: Only limited data on the seroprevalence of herpes simplex virus type 2 (HSV-2) are available from European countries. Until recently, serologic tests for HSV-2 serotyping have been hampered by cross-reactivity to type-common antigens. The present study aims at providing data on the prevalence of HSV-2 infection in a group of STD clinic attendees using a reliable type-specific immunoassay. GOAL: To evaluate the seroprevalence of HSV-2 and the accumulated incidence of clinical genital herpes infection in a sample of Spanish sexually transmitted disease (STD) clinic attendees. STUDY DESIGN: The study consisted of two parts. First, a cross-sectional study of HSV-2 seroprevalence was conducted in patients with STDs. Second, a prospective cohort study was undertaken to evaluate the accumulated incidence of infection by HSV-2 and of clinical episodes of genital herpes in HSV-2-negative patients included in the first study during a follow-up period of 6 to 18 months. RESULTS: Of the 374 patients (129 men, 245 women) studied, 25% were seropositive for HSV-2 (12% of men, 30% of women). Antibodies to HSV-2 were related to female gender (odds ratio, 2.7; P < 0.001) and to the number of sexual partners (odds ratio, 4.1; P < 0.001). Fifty-two percent of patients (145 of 281 patients) who were initially seronegative returned to the clinic for a second serologic testing, of whom 1% (2 of 145 patients) had seroconverted. None of the patients developed genital herpes during the follow-up period. CONCLUSION: The relatively high seroprevalence (25%) and the low rate (4%) of HSV-2 previously reported in the general population in Spain suggest that the virus circulation may be restricted to certain risk groups. Therefore, future healthcare measures may target specific groups, such as patients with STDs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11196047&dopt=Abstract herpes medicine



herpes
[Intensity of the humoral immune response to herpes viruses as an indicator the body immune deficiency]

[Article in Russian]

Kologrivova EN, Lebedev MP, Borisenko AV, Choinzonov EL, Isaeva TM.

Siberian Medical University, Research Institute of Oncology, Tomsk Research Center, Russian Acad. Med. Sci., Tomsk, Russia.

The state of the local immunity system of the oral cavity was studied by the level of saliva immunoglobulins in patients with different processes on their mucous membranes: herpetic infection, respiratory allergosis and malignant tumors of the mouth cavity and the laryngopharynx. The suppression of the production of sIgA, was accompanied by the enhanced production of antibodies to the most widespread herpes viruses (herpes simplex virus, cytomegalovirus and Epstein-Barr virus). The maximum levels of serum IgG to herpes viruses were determined in patients with malignant tumors. The role of herpes viruses in the pathogenesis of immunodeficient states is discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11210635&dopt=Abstract herpes medicine



herpes
Herpesvirus alkaline deoxyribonuclease; a possible candidate as a novel target for anti-herpes virus therapy.

Chiba A, Ogasawara M, Yoshida I, Knox YM, Suzutani T.

Department of Microbiology, Asahikawa Medical College, Japan.

Herpesvirus alkaline deoxyribonucrease (DNase) is coded in the genome of all herpes virus species determined total sequence and is conserved in structure. In order to determine whether the enzyme could be a target for a novel antiherpes virus therapy, the anti-herpes simplex virus type 1 (HSV-1) activity of antisense oligonucleotide for HSV-1 alkaline DNase was studied. Six antisense phosphorothioate oligonucleotides, targeted to an internal AUG start codon, were designed and evaluated. One of the oligonucleotides, UL12-4, inhibited wild type and thymidine kinase-deficient HSV-1 replication to 21.5 and 19.5% at 40 microM, respectively. The quantity of alkaline DNase mRNA and DNase activity in HSV-1-infected Vero cells was reduced to one eighth and 66.9% of control, respectively, by treatment with 40 microM of UL12-4, but no effect was observed on the quantity of HSV-1 glycoprotein H mRNA (gamma2 gene) or on the replication of Vero cells. These results indicate that UL12-4 inhibits HSV-1 replication by decreasing the amount of alkaline DNase mRNA. The herpes virus alkaline DNase could be a novel target for anti-herpes virus drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11211313&dopt=Abstract herpes medicine