Neuropathogenesis of herpesvirus papio 2 in mice parallels infection with Cercopithecine herpesvirus 1 (B virus) in humans

Abstract

Cercopithecine herpesvirus 1 (monkey B virus; BV) produces extremely severe and usually fatal infections when transmitted from macaque monkeys to humans. Cercopithecine herpesvirus 16 (herpesvirus papio 2; HVP2) is very closely related to BV, yet cases of human HVP2 infection are unknown. However, following intramuscular inoculation of mice, HVP2 rapidly invades the peripheral nervous system and ascends the central nervous system (CNS) resulting in death, very much like human BV infections. In this study, the neurovirulence of HVP2 in mice was further evaluated as a potential model system for human BV infections. HVP2 was consistently neurovirulent when administered by epidermal scarification, intracranial inoculation and an eye splash. Quantitative real-time PCR, histopathology and immunohistochemistry were used to follow the temporal spread of virus following skin scarification and to compare the pathogenesis of neurovirulent and apathogenic isolates of HVP2. Apathogenic isolates were found to be capable of reaching the CNS but were extremely inefficient at replicating within the CNS. It is concluded that neurovirulent strains of HVP2 exhibit a pathogenesis in mice that parallels that observed in human BV infections and that this model system may prove useful in dissecting the viral determinants underlying the extreme severity of zoonotic BV infections.