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)

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 > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
65652	1	The role of ubiquitin and ubiquitin-like proteins during viral infection	Chris Boutell	Medical Research Council (MRC)	MC_UU_12014/5	MVLS III - CENTRE FOR VIRUS RESEARCH