Establishment of HSV1 latency in immunodeficient mice facilitates efficient in vivo reactivation

PLoS Pathogens
Chandran RamakrishnaEdouard M Cantin

Abstract

The establishment of latent infections in sensory neurons is a remarkably effective immune evasion strategy that accounts for the widespread dissemination of life long Herpes Simplex Virus type 1 (HSV1) infections in humans. Periodic reactivation of latent virus results in asymptomatic shedding and transmission of HSV1 or recurrent disease that is usually mild but can be severe. An in-depth understanding of the mechanisms regulating the maintenance of latency and reactivation are essential for developing new approaches to block reactivation. However, the lack of a reliable mouse model that supports efficient in vivo reactivation (IVR) resulting in production of infectious HSV1 and/or disease has hampered progress. Since HSV1 reactivation is enhanced in immunosuppressed hosts, we exploited the antiviral and immunomodulatory activities of IVIG (intravenous immunoglobulins) to promote survival of latently infected immunodeficient Rag mice. Latently infected Rag mice derived by high dose (HD), but not low dose (LD), HSV1 inoculation exhibited spontaneous reactivation. Following hyperthermia stress (HS), the majority of HD inoculated mice developed HSV1 encephalitis (HSE) rapidly and synchronously, whereas for LD inoculated mice rea...Continue Reading

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Oct 21, 2016·Cell Reports·Jonatan EnkOfer Mandelboim
Apr 14, 2017·Journal of Virology·Rebecca G Edwards, Richard Longnecker
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Methods Mentioned

BETA
flow cytometry
transgenic
PCR
xenografts
in vitro transcription

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