PML-NB-dependent type I interferon memory results in a restricted form of HSV latency

Suzich, J. B., Cuddy, S. R., Baidas, H., Dochnal, S., Ke, E., Schinlever, A. R., Babnis, A., Boutell, C. and Cliffe, A. R. (2021) PML-NB-dependent type I interferon memory results in a restricted form of HSV latency. EMBO Reports, 22(9), e52547. (doi: 10.15252/embr.202152547) (PMID:34197022)

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Abstract

Herpes simplex virus (HSV) establishes latent infection in long-lived neurons. During initial infection, neurons are exposed to multiple inflammatory cytokines but the effects of immune signaling on the nature of HSV latency are unknown. We show that initial infection of primary murine neurons in the presence of type I interferon (IFN) results in a form of latency that is restricted for reactivation. We also find that the subnuclear condensates, promyelocytic leukemia nuclear bodies (PML-NBs), are absent from primary sympathetic and sensory neurons but form with type I IFN treatment and persist even when IFN signaling resolves. HSV-1 genomes colocalize with PML-NBs throughout a latent infection of neurons only when type I IFN is present during initial infection. Depletion of PML prior to or following infection does not impact the establishment latency; however, it does rescue the ability of HSV to reactivate from IFN-treated neurons. This study demonstrates that viral genomes possess a memory of the IFN response during de novo infection, which results in differential subnuclear positioning and ultimately restricts the ability of genomes to reactivate.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boutell, Dr Chris
Creator Roles:
Boutell, C.Resources, Writing – review and editing
Authors: Suzich, J. B., Cuddy, S. R., Baidas, H., Dochnal, S., Ke, E., Schinlever, A. R., Babnis, A., Boutell, C., and Cliffe, A. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Journal Name:EMBO Reports
Publisher:Wiley
ISSN:1469-221X
ISSN (Online):1469-3178
Published Online:01 July 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in EMBO Reports 22(9): e52547
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656521The role of ubiquitin and ubiquitin-like proteins during viral infectionChris BoutellMedical Research Council (MRC)MC_UU_12014/5MVLS III - CENTRE FOR VIRUS RESEARCH