Excretion of B virus in monkeys and evidence of genital infection

Zwartouw, H. T.; Boulter, Etienne

doi:10.1258/002367784780864929

Cited by 58 publications

(25 citation statements)

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“…In this respect, identification of analogous proteins and/or related structural regions (or antigenic determinants) on proteins of closely related viruses may serve not only to identify structurally analogous proteins of less-well characterized viruses but functionally or pathogenically analogous viral polypeptides of general biological significance as well. In addition, the high fatality rate associated with B virus infections in humans and the high natural infection rate of this virus in macaques often without any outward signs of disease [28,57] presents a very real problem for personnel handling these species. The extensive cross-reactivity of B virus and HSV in neutralization and ELISA assays has made the serological identification of asymptomatic and/or latently infected macaques and the rapid differential diagnosis of human B virus infections difficult [27,53,54].…”

Section: Introductionmentioning

confidence: 99%

Relatedness of glycoproteins expressed on the surface of simian herpesvirus virions and infected cells to specific HSV glycoproteins

Eberle

Black

Hilliard

1989

Archives of Virology

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The antigenic relatedness of the surface glycoprotein antigens of six herpesviruses indigenous to human and nonhuman primates was examined. Binding of anti-viral sera to viral antigens expressed on the surface of infected cells demonstrated that the surface antigens of herpes simplex virus type 1 (HSV 1), HSV 2, simian agent 8 (SA8), and Herpesvirus simiae (B virus) exhibit extensive cross-reactivity. Surface antigens of two viruses isolated from South American primates, H. saimiri 1 (HVS 1) and H. ateles 1 (HVA 1), were comparatively more virus-specific in their antigenic reactivity. Endpoint neutralization tests performed in the presence and absence of complement confirmed these results. Immunoprecipitation of viral proteins was used to identify those representing cross-reactive surface antigens. A glycoprotein of approximately 110,000-125,000 Daltons (110-125 k) was immunoprecipitated from cells infected with each of the six primate herpesvirus by antisera to each of the viruses. Using monospecific antisera, these glycoproteins were shown to be antigenically related to the gB glycoproteins of HSV. Although these glycoproteins were antigenically conserved among all six viruses, antibodies to the gB glycoproteins did not cross-neutralize heterologous viruses. A glycoprotein of approximately 60-70 k was precipitated from HSV 1, HSV 2, SA8, and B virus infected cells by antisera to each of these four viruses. These SA8 and B virus glycoproteins were shown to be antigenically related to the gD glycoproteins of HSV 1 and HSV 2 and to be involved in cross-neutralization among these viruses. Antisera to HVS 1 and HVA 1 did not recognize these gD glycoproteins nor was a glycoprotein of similar molecular weight precipitable from HVS 1 or HVA 1 infected cells by antisera to the other four viruses. Southern blot hybridizations using probes for HSV glycoprotein genes confirmed the conservation of the gB glycoproteins among all the simian viruses and of the gD gene in SA8 and B virus. A glycoprotein of approximately 75-80 k was, however, precipitated from HVS 1 and HVA 1 infected cells by antisera to either of these two viruses. In addition, at least one glycoprotein which appeared to be predominantly virus-specific in its reactivity was identified for five of the viruses.

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Section: Introductionmentioning

confidence: 99%

Relatedness of glycoproteins expressed on the surface of simian herpesvirus virions and infected cells to specific HSV glycoproteins

Eberle

Black

Hilliard

1989

Archives of Virology

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“…In its natural host, macaque monkeys, B virus (Macacine herpesvirus 1; Simplexvirus, Herpesviridae) causes lesions on epithelial surfaces (2,33) and establishes reactivatable latent infection in sensory neurons (30,37), like herpes simplex virus (HSV) in humans. B virus often results in severe pathogenesis, including paralysis, encephalitis, and in many cases, rapid death, following infection of humans (reviewed in reference 22).…”

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Inhibition of B Virus (Macacine herpesvirus1) by Conventional and Experimental Antiviral Compounds

Krug

Schinazi

Hilliard

2010

Antimicrob Agents Chemother

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B virus infection of humans results in high morbidity and mortality in as many as 80% of identified cases.The main objective of this study was to conduct a comparative analysis of conventional and experimental antiviral drug susceptibilities of B virus isolates from multiple macaque species and zoonotically infected humans. We used a plaque reduction assay to establish the effective inhibitory doses of acyclovir, ganciclovir, and vidarabine, as well as those of a group of experimental nucleoside analogs with known anti-herpes simplex virus activity. Four of the experimental drugs tested were 10-to 100-fold more potent inhibitors of B virus replication than conventional antiviral agents. Drug efficacies were similar for multiple B virus isolates tested, with variations within 2-fold of the median effective concentration (EC 50 ) for each drug, and each EC 50 was considerably lower than those for B virus thymidine kinase (TK) mutants. We observed no differences in the viral TK amino acid sequence between B virus isolates from rhesus monkeys and those from human zoonoses. Differences in the TK protein sequence between cynomolgus and pigtail macaque B virus isolates did not affect drug sensitivity except in the case of one compound. Taken together, these data suggest that future B virus zoonoses will respond consistently to conventional antiviral treatment. Further, the considerably higher potency of FEAU (2-fluoro-5-ethyl-Ara-U) than of conventional antiviral drugs argues for its compassionate use in advanced human B virus infections.In its natural host, macaque monkeys, B virus (Macacine herpesvirus 1; Simplexvirus, Herpesviridae) causes lesions on epithelial surfaces (2, 33) and establishes reactivatable latent infection in sensory neurons (30, 37), like herpes simplex virus (HSV) in humans. B virus often results in severe pathogenesis, including paralysis, encephalitis, and in many cases, rapid death, following infection of humans (reviewed in reference 22). Nearly all reported cases of B virus zoonosis have been associated with individuals handling macaques during the course of research or technology development (33). Five fatalities, along with at least 23 cases in which the patient survived, have occurred in the past 20 years, underscoring that zoonotic infections remain a problem in the laboratory animal environment (7-9).The CDC's B Virus Working Group currently recommends treatment of confirmed zoonotic infections with herpesvirusspecific antiviral drugs, including acyclovir (ACV) and ganciclovir (GCV) (10). Both agents in this class of compounds are phosphorylated to active form by virus-encoded thymidine kinase (TK). The resulting nucleoside triphosphate analog inhibits viral DNA replication by termination of chain elongation and by direct inhibition of herpesvirus DNA polymerase (24). While ACV is effective against B virus both in cell culture and in animal models (6), the dose required for 50% plaque reduction is more than 10-fold higher for B virus than for HSV type 1 (HSV-1) (38). GCV is twice as pot...

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“…Unfortunately, a direct diagnosis of infection by virus detection (cell culture or PCR) is impossible in most cases, since, similar to other alphaherpesviruses, B virus establishes a lifelong latency in sensory ganglia of macaques and seldom reactivates (9,53,58). Current diagnoses of B virus infections in humans and monkeys rely mainly on the detection of serum antibodies to B virus proteins.…”

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confidence: 99%

Production of Herpes B Virus Recombinant Glycoproteins and Evaluation of Their Diagnostic Potential

et al. 2005

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B virus (cercopithecine herpesvirus 1) is the only deadly alphaherpesvirus that is zoonotically transmissible from macaques to humans. The detection of humoral immune responses is the method of choice for the rapid identification of B virus-infected animals. We evaluated the diagnostic potential of recombinant B virus glycoproteins for the detection of immunoglobulin G (IgG) antibodies in monkey and human sera. Glycoproteins B, C, and E and secreted (sgG) and membrane-associated (mgG) segments of glycoprotein G (gG) were expressed in the baculovirus expression system, while gD was expressed in CHO cells. We developed recombinant protein-based IgG enzyme-linked immunosorbent assays (ELISAs) and compared their diagnostic efficacies by using B virus antibody-negative (n ‫؍‬ 40) and -positive (n ‫؍‬ 75) macaque sera identified by a whole antigenbased ELISA and Western blotting. The diagnostic sensitivities of the gB-, gC-, gD-, and mgG-ELISAs were 100, 97.3, 88.0, and 80.0%, respectively. The specificities of the gB-, gC-, and gD-ELISAs and of the mgG-ELISA were 100 and 97.5%, respectively. In contrast, the sensitivities and specificities of sgG-and gE-ELISAs were low, suggesting that sgG and gE are less effective diagnostic antigens. Sera from nonmacaque monkeys crossreacted with gB, gC, and gD, and only baboon sera reacted weakly with mgG. Human herpes simplex virus type 1 (HSV-1)-and HSV-2-positive sera pools reacted with gB and gD, whereas sera from B virus-infected individuals reacted with all four antigens. These data indicate that gB, gC, gD, and mgG have a high diagnostic potential for B virus serodiagnosis in macaques, whereas mgG may be a valuable antigen for discrimination between antibodies induced by B virus and those induced by other, closely related alphaherpesviruses, including HSV-1 and -2.Human infection with B virus (also called cercopithecine herpesvirus 1, monkey B virus, and herpes B virus) is the most feared occupational hazard among individuals working with macaque monkeys, since fatality is often the outcome of infection, which proceeds in the absence of effective antiviral therapy (25,56). The use of macaques in research has been steadily growing over the last decade and is expected to rise quickly in the near future due to the increasing demands for these animals for use in HIV/AIDS investigations, vaccine trials, drug testing, and research into bioterrorism agents. As macaque usage increases, frequencies of human exposures to B virus are increasing as well. Rapid and accurate diagnostic tests are urgently needed to aid in the early identification of clinical cases, which is essential for a timely initiation of antiviral therapies in zoonotically infected humans. In addition to human diagnostics, enhanced assays are required for monitoring specific-pathogen-free (SPF) macaque colonies established by the National Institutes of Health for the breeding of B virusfree animals (55), as these animals often demonstrate only very low levels of antibody.Unfortunately, a direct diagnosis of infectio...

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Excretion of B virus in monkeys and evidence of genital infection

Cited by 58 publications

References 4 publications

Relatedness of glycoproteins expressed on the surface of simian herpesvirus virions and infected cells to specific HSV glycoproteins

Relatedness of glycoproteins expressed on the surface of simian herpesvirus virions and infected cells to specific HSV glycoproteins

Inhibition of B Virus (Macacine herpesvirus1) by Conventional and Experimental Antiviral Compounds

Production of Herpes B Virus Recombinant Glycoproteins and Evaluation of Their Diagnostic Potential

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