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Published on: June 14, 2020
Neuropathogenesis of herpesvirus papio 2 in mice parallels infection with Cercopithecine herpesvirus 1 (B virus) in
Kristin M Rogers1, Jerry W Ritchey1, Mark Payton1
1Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, 250 McElroy Hall, Stillwater, OK 74078-2007, USA.
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.
Insights
Cercopithecine herpesvirus 16 (HVP2) shows neurovirulence in mice, mirroring human monkey B virus (BV) infections. This mouse model can help study the severe zoonotic BV infections.
Area of Science:
- Virology
- Neuroscience
- Zoonotic Diseases
Background:
- Cercopithecine herpesvirus 1 (monkey B virus; BV) causes severe, often fatal, human infections.
- Cercopithecine herpesvirus 16 (HVP2), closely related to BV, has unknown human infection cases.
- HVP2 causes fatal central nervous system (CNS) infections in mice after peripheral inoculation.
Purpose of the Study:
- Evaluate HVP2 neurovirulence in mice as a model for human BV infections.
- Investigate viral determinants of zoonotic BV infection severity.
Main Methods:
- Mice were inoculated with HVP2 via epidermal scarification, intracranial inoculation, and eye splash.
- Quantitative real-time PCR, histopathology, and immunohistochemistry tracked viral spread.
- Neurovirulent and apathogenic HVP2 isolates were compared.
Main Results:
- HVP2 was consistently neurovirulent across different inoculation routes.
- Apathogenic HVP2 isolates reached the CNS but replicated inefficiently.
- Neurovirulent HVP2 strains demonstrated a pathogenesis in mice similar to human BV infections.
Conclusions:
- Neurovirulent HVP2 strains in mice provide a relevant model for studying human BV infections.
- This model system aids in dissecting viral factors contributing to BV's zoonotic severity.
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