Detection systems for antibody responses against herpesB virus.

Stefan Pöhlmann,Jens Gruber,Stefan Schneider,Michael Winkler,Astrid Krüger,Artur Kaul,Wali Hafezi

doi:10.5194/pb-4-9-2017

Abstract

Herpes B virus (BV) infection is highly prevalent among adult Asian macaques and rarely causes severe disease in infected animals. In contrast, BV infection of humans can induce fatal encephalitis in the absence of treatment. Therefore, the development of diagnostic tests for specific and sensitive detection of antibodies against BV is an important task. The cross-reactivity of antibodies against BV with related simplex viruses of other primates may afford an opportunity to obtain sensitive detection systems without the need to work with the highly pathogenic BV. Moreover, it has been proposed that use of recombinant viral glycoproteins may allow for a detection of antibody responses against BV with high specificity. However, limited data are available for both approaches to BV diagnostic. Here, we report that simian agent 8 (SA8; infects African green monkeys)- and herpesvirus papio 2 (HVP-2; infects baboons)-infected cells allow for a more sensitive detection of antibody responses against BV in macaques than lysates of herpes simplex virus type 1 and 2 (HSV-1/2; infect humans)-infected cells and a commercial HSV ELISA (Enzygnost® Anti-HSV/IgG). In addition, we show that sera from BV-infected macaques frequently contain antibodies against the recombinant BV glycoprotein gD (BV gD) that has been previously proposed as a diagnostic target for discriminating BV- and HSV-induced antibodies. However, we found that antibodies of some HSV-infected human patients also reacted with BV gD. In contrast, only sera of HSV-1- and HSV-2-infected humans, but not sera from BV-infected macaques, reacted with HSV-1/2 gG. Collectively, these results suggest that both SA8 and HVP-2 allow for sensitive and comparable detection of BV-directed antibody responses in macaques and that the combination of BV gD and HSV-1/2 gG needs to be complemented by a least one additional viral glycoprotein for reliable discrimination between antibody responses against BV and HSV-1/2 in humans.

Highlights

Herpesviruses are large, enveloped DNA viruses that infect diverse vertebrate and invertebrate hosts
The prevention of human exposure to B virus (BV), specific detection of BV infection of humans and establishment of BV-free macaque colonies (Yee et al, 2016) depend on the availability of diagnostic systems, which allow for the detection of antibodies against simplex viruses of human and non-human primates (NHPs) origin with high sensitivity and specificity
Our study shows that simian agent 8 (SA8)- and HPV-2-infected cells allow for the detection of antibodies raised against BV with higher sensitivity than HSV1- and HSV-2-infected cells

Summary

Introduction

Herpesviruses are large, enveloped DNA viruses that infect diverse vertebrate and invertebrate hosts. A hallmark of herpesviruses is the latent infection of certain host cells, in which the viruses can persist in a dormant form for long time periods (Koyuncu et al, 2013). Herpes simplex virus type 1 (HSV-1) and HSV-2 infect cells in the oral and genital mucosa and may cause lesions in these tissues, which usually heal without scarring (Delaney et al, 2014; Xu et al, 2006). HSV-1 and HSV-2 infection rarely causes encephalitis or other serious complications despite the pronounced neurotropism and high prevalence of both viruses in the human population (Delaney et al, 2014; Xu et al, 2006). Herpes B virus (BV, Macacine herpesvirus 1, termed B virus, herpesvirus simiae or Cercopithecine herpesvirus 1), the HSV homologue of macaques (Elmore and Eberle, 2008; Hilliard, 2007; Huff and Barry, 2003), is highly prevalent in adult animals (Weigler et al, 1990, 1993) but disseminated infection and Published by Copernicus Publications on behalf of the Deutsches Primatenzentrum GmbH (DPZ)

Methods

Results

Conclusion