herpes
Glycoprotein gD of MDV lacks functions typical for alpha-herpes virus gD homologues.

Zelnik V, Majerciak V, Szabova D, Geerligs H, Kopacek J, Ross LJ, Pastorek J.

Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic. viruzelo nic.savba.sk

Glycoprotein D (gD) belongs to family of conserved structural proteins of alpha-herpes viruses. During productive infection of cells by herpes simplex virus 1 (HSV-1) gD has several important functions, is involved in virus penetration to and release from infected cells and is one of main targets of neutralizing antibodies. Similar functions are shared also by other alpha-herpes virus gD homologues. Surprisingly, in previous studies it was found that MDV gD expression could not be detected during infection in vitro using immunological methods. In this study we have analyzed expression of MDV gD and its biological consequences. In vitro expression using rabbit reticulocyte lysate and/or overexpression in transfected cells showed that the second ATG codon is required for synthesis of mature, glycosylated gD. In addition, it was found that gD overexpression is neither toxic for transfected cells nor is involved in membrane fusion. After MDV infection of a proprietary cell line stably transfected with plasmid overexpressing MDV gD, no viral particles could be found in culture. On the other hand, cells overexpressing the MDV gD were sensitive to MDV infection in similar way as parental, non-transfected cells. From our study and results of other authors we propound the following conclusions: (i) MDV gD expression is blocked during in vitro infection at transcription level; (ii) MDV gD is lacking many important functions characteristic for other alpha-herpes virus gD homologues; (iii) overexpression of single MDV gD does not result in production of mature infectious MDV particles.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10696439&dopt=Abstract herpes medicine



herpes
Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus, type 1.

Xia G, Chen J, Tiwari V, Ju W, Li JP, Malmstrom A, Shukla D, Liu J.

Cell and Molecular Biology, Biomedical Center C13, Lund University, Lund S-22184, Sweden.

Heparan sulfate 3-O-sulfotransferase transfers sulfate to the 3-OH position of a glucosamine residue of heparan sulfate (HS) to form 3-O-sulfated HS. The 3-O-sulfated glucosamine residue contributes to two important biological functions of HS: binding to antithrombin and thereby carrying anticoagulant activity, and binding to herpes simplex viral envelope glycoprotein D to serve as an entry receptor for herpes simplex virus 1. A total of five HS 3-O-sulfotransferase isoforms were reported previously. Here we report the isolation and characterization of a novel HS 3-O-sulfotransferase isoform, designated as HS 3-O-sulfotransferase isoform 5 (3-OST-5). 3-OST-5 cDNA was isolated from a human placenta cDNA library and expressed in COS-7 cells. The disaccharide analysis of 3-OST-5-modified HS revealed that 3-OST-5 generated at least three 3-O-sulfated disaccharides as follows: IdoUA2S-AnMan3S, GlcUA-AnMan3S6S, and IdoUA2S-AnMan3S6S. Transfection of the plasmid expressing 3-OST-5 rendered wild type Chinese hamster ovary cells susceptible to the infection by herpes simplex virus 1, suggesting that 3-OST-5-modified HS serves as an entry receptor for herpes simplex virus 1. In addition, 3-OST-5-modified HS bound to herpes simplex viral envelope protein glycoprotein D. Furthermore, we found that 3-OST-5-modified HS also bound to antithrombin, suggesting that 3-OST-5 also produces anticoagulant HS. In summary, our results indicate that a new member of 3-OST family generates both anticoagulant HS and an entry receptor for herpes simplex virus 1. These results provide a new insight regarding the mechanism for the biosynthesis of biologically active HS.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12138164&dopt=Abstract herpes medicine



herpes
[Herpes simplex virus type 1 and 2 in Switzerland]

[Article in German]

Laubereau B, Zwahlen M, Neuenschwander B, Heininger U, Schaad UB, Desgrandchamps D.

Infektiologie-/Vakzinologie-Zentrum, Universitats-Kinderspital beider Basel.

A worldwide increase in the incidence of genital herpes infections has been described in recent years. Transmission of the herpes simplex virus type 2 (HSV-2) by asymptomatic seropositive subjects is considered to be a relevant mode of infection. The seroprevalence of HSV-2 varies considerably between different populations. In Europe, data are scarce and the epidemiological situation in Switzerland is unknown. In 1997 we performed serological examinations in 151 adult volunteers (87% between 20 and 49 years of age) of a low-risk population from the region of Basel with no history of genital herpes or any other sexually transmitted disease. The overall seroprevalence of HSV-1 was 77% and an annual seroconversion rate of 4.6% (95% CI: 3.8-5.6) was estimated for both sexes. Of the 51 subjects with no symptoms of orolabial herpes, 25 (49%) proved to be HSV-1 seropositive. In contrast, of 91 patients with symptoms of orolabial herpes, 90 (97%) had serum antibodies against HSV-1. The seroprevalence of HSV-2 was 14.6% for women (n = 89) and 8.1% for men (n = 62). The annual seroconversion rate was estimated to be 0.61% (95% CI: 0.14-1.4) for women and 0.49% (95% CI: 0.09-1.4) for men for the period after 1985 (when "safer sex" and the use of condoms were promoted). Our results indicate the significance of herpes simplex virus type 2 infections in Switzerland. More detailed studies are needed to describe the epidemiology of HSV-2 infections more reliably, especially in view of progress in the development of vaccines against HSV infections.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10701231&dopt=Abstract herpes medicine



herpes
High prevalence of herpes simplex virus type 2 in acute retinal necrosis syndrome associated with herpes simplex virus in Japan.

Itoh N, Matsumura N, Ogi A, Nishide T, Imai Y, Kanai H, Ohno S.

Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Japan. taro med.yokohama-cu.ac.jp

PURPOSE: To determine the type of herpes simplex virus in acute retinal necrosis syndrome associated with herpes simplex virus. METHODS: Herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were examined by polymerase chain reaction in intraocular specimens from 16 patients with acute retinal necrosis syndrome. Anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 type-specific antibodies in serum from the patients were detected by enzyme immunoassay. RESULTS: Of 16 patients with acute retinal necrosis syndrome, seven were polymerase chain reaction positive for herpes simplex virus type 2 and nine were positive for varicella-zoster virus. Anti-herpes simplex virus type 2 antibody was positive and anti-herpes simplex virus type 1 antibody was negative in the sera of the seven patients with herpes simplex virus type 2 DNA-positive acute retinal necrosis syndrome. In contrast, anti-herpes simplex virus type 2 antibody was absent in all nine varicella-zoster virus DNA-positive acute retinal necrosis syndrome patients. CONCLUSION: Herpes simplex virus type 2 has been demonstrated to be the major causative agent in acute retinal necrosis syndrome associated with herpes simplex virus by molecular biological and serological methods. Negative preexisting anti-herpes simplex virus type 1 antibody may play an important role in acute retinal necrosis syndrome associated with herpes simplex virus type 2.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10704570&dopt=Abstract herpes medicine



herpes
Distinctions between bovine herpes virus 1 and herpes simplex virus type 1 VP22 tegument protein subcellular associations.

Harms JS, Ren X, Oliveira SC, Splitter GA.

Department of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706-1581, USA. harms ahabs.wisc.edu

The alphaherpes virus tegument protein VP22 has been characterized with multiple traits including microtubule reorganization, nuclear localization, and nonclassical intercellular trafficking. However, all these data were derived from studies using herpes simplex virus type 1 (HSV-1) and may not apply to VP22 homologs of other alphaherpes viruses. We compared subcellular attributes of HSV-1 VP22 (HVP22) with bovine herpes virus 1 (BHV-1) VP22 (BVP22) using green fluorescent protein (GFP)-fused VP22 expression vectors. Fluorescence microscopy of cell lines transfected with these constructs revealed differences as well as similarities between the two VP22 homologs. Compared to that of HVP22, the BVP22 microtubule interaction was much less pronounced. The VP22 nuclear interaction varied, with a marbled or halo appearance for BVP22 and a speckled or nucleolus-bound appearance for HVP22. Both VP22 homologs associated with chromatin at various stages of mitosis and could traffic from expressing cells to the nuclei of nonexpressing cells. However, distinct qualitative differences in microtubule, nuclear, and chromatin association as well as trafficking were observed. The differences in VP22 homolog characteristics revealed in this study will help define VP22 function within HSV-1 and BHV-1 infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10708447&dopt=Abstract herpes medicine



herpes
Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons.

Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, Krieger JN, Corey L.

Department of Medicine, University of Washington, Seattle 98122, USA. annawald u.washington.edu

BACKGROUND: Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection. METHODS: We conducted a prospective study to investigate genital shedding of HSV among 53 subjects who had antibodies to HSV-2 but who reported having no history of genital herpes, and we compared their patterns of viral shedding with those in a similar cohort of 90 subjects with symptomatic HSV-2 infection. Genital secretions of the subjects in both groups were sampled daily and cultured for HSV for a median of 94 days. RESULTS: HSV was isolated from the genital mucosa in 38 of the 53 HSV-2-seropositive subjects (72 percent) who reported no history of genital herpes, and HSV DNA was detected by the polymerase-chain-reaction assay in cultures prepared from genital mucosal swabs in 6 additional subjects. The rate of subclinical shedding of HSV in the subjects with no reported history of genital herpes was similar to that in the subjects with such a history (3.0 percent vs. 2.7 percent). Of the 53 subjects who had no reported history of genital herpes, 33 (62 percent) subsequently reported having typical herpetic lesions; the duration of their recurrences in these subjects was shorter (median, three days vs. five days; P<0.001) and the frequency lower (median, 3.0 per year vs. 8.2 per year; P<0.001) than in the 90 subjects with previously diagnosed symptomatic infection. Only 1 of these 53 subjects had no clinical or virologic evidence of HSV infection. CONCLUSIONS: Seropositivity for HSV-2 is associated with viral shedding in the genital tract, even in subjects with no reported history of genital herpes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10727588&dopt=Abstract herpes medicine



herpes
[Anti-herpes chemotherapy]

[Article in French]

Ingrand D.

Laboratoire de bacteriologie-virologie-hygiene CHU, hopital Robert-Debre, Reims.

With the increasing number of immunocompromised patients over the last two decades, disease pattern caused by Herpesviridae has changed. More virulent, more severe, herpes virus diseases are more frequently treated and consequently the drug-resistant herpes virus mutants have arisen in the clinic. All these events justify to explore future directions in drug development and herpesviral research as antisens strategy or immunotherapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10731809&dopt=Abstract herpes medicine



herpes
Characterization of the human herpes virus 8 (Kaposi's sarcoma-associated herpes virus) oncogene, kaposin (ORF K12).

Muralidhar S, Veytsmann G, Chandran B, Ablashi D, Doniger J, Rosenthal LJ.

Department of Microbiology, Georgetown University Medical Center, 3900 Reservoir Road N.W., Washington, DC, USA.

BACKGROUND: Human herpes virus 8 (HHV-8) has been implicated in the etiology of Kaposi's sarcoma (KS), a highly angiogenic tumor of complex histology, and two lymphoproliferative diseases, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). A number of HHV-8 encoded genes have been proposed to be involved in the pathogenesis of KS and PEL and a few have been shown to be oncogenic in heterologous systems (Reyes GR, LaFemina R, Hayward SD, Hayward GS. Morphological transformation by DNA fragments of human herpes viruses: evidence for two distinct transforming regions in herpes simplex virus types 1 and 2 and lack of correlation with biochemical transfer of the thymidine kinase gene. Cold Spring Harbor Symp Quant Biol 1980;44:629-641; Moore PS, Boshoff C, Weiss RA, Chang Y. Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science 1996;274:1739-1744; Cheng EH, Nicholas J, Bellows DS, Hayward GS, Guo HG, Reitz MS, Hardwick JM. A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpes virus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci USA 1997;94:690-694; Li M, Lee H, Yoon DW, Albrecht JC, Fleckenstein B, Neipel F, Jung JU. Kaposi's sarcoma-associated herpes virus encodes a functional cyclin. J Virol 1997;71:1984-1991; Neipel F, Albrecht J-C, Fleckenstein B. Cell-homologous genes In the Kaposi's sarcoma-associated rhadinovirus human herpes virus 8: determinants of its pathogenicity? J Virol 1997;71:4187-4192; Nicholas J, Ruvolo VR, Burns WH, Sandford G, Wan X, Ciufo D, Hendrickson SB, Guo HG, Hayward GS, Reitz MS. Kaposi's sarcoma-associated human herpes virus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nat Med 1997;3:287-292; Nicholas J, Zong J, Alcendor DJ, Ciufu DM, Poole LJ, Sarisky RT, Chiuo C, Zhang X, Wan X, Guo H, Reitz MS, Hayward GS. Novel organizational features, captured cellular genes, and strain variability within the genome of KSHV/HHV-8. JNCI Monographs 1998;23:79-88; Muralidhar S, Pumfery AM, Hassani M, Sadaie MR, Azumi N, Kishishita M, Brady JN, Doniger J, Medveczky P, Rosenthal LJ. Identification of kaposin (ORF K12) as a human herpes virus 8 (Kaposi's sarcoma associated herpes virus) transforming gene. J Virol 1998;72:4980-4988). The kaposin gene (ORF K12) encoded by the abundant latency-associated HHV-8 transcript, T0.7, has been previously shown to induce tumorigenic transformation of Rat-3 cells (Muralidhar S, Pumfery AM, Hassani M, Sadaie MR, Azumi N, Kishishita M, Brady JN, Doniger J, Medveczky P, Rosenthal LJ. Identification of kaposin (ORF K12) as a human herpes virus 8 (Kaposi's sarcoma associated herpes virus) transforming gene. J Virol 1998;72:4980-4988). The current study is a further characterization of kaposin protein. OBJECTIVES: Characterization of kaposin expression in transformed and tumor-derived Rat-3 cells as well as PEL cell lines, BCBL-1, BC-3 and KS-1 and analysis of mechanism(s) of transformation. DESIGN: The presence of kaposin DNA in transformed cells was determined by fluorescent in situ hybridization (FISH). Expression of kaposin protein was analyzed by Western blot analysis and indirect immunofluorescence assay (IFA). (ABSTRACT TRUNCATED)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10738139&dopt=Abstract herpes medicine