Dynamic response of IFI16 and promyelocytic leukemia nuclear body components to herpes simplex virus 1 infection

Everett, R. D. (2016) Dynamic response of IFI16 and promyelocytic leukemia nuclear body components to herpes simplex virus 1 infection. Journal of Virology, 90(1), pp. 167-179. (doi: 10.1128/jvi.02249-15) (PMID:26468536) (PMCID:PMC4702556)

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Abstract

Intrinsic immunity is an aspect of antiviral defense that operates through diverse mechanisms at the intracellular level through a wide range of constitutively expressed cellular proteins. In the case of herpesviruses, intrinsic resistance involves the repression of viral gene expression during the very early stages of infection, a process that is normally overcome by viral tegument and/or immediate-early proteins. Thus, the balance between cellular repressors and virus-counteracting proteins determines whether or not a cell becomes productively infected. One aspect of intrinsic resistance to herpes simplex virus 1 (HSV-1) is conferred by components of promyelocytic leukemia nuclear bodies (PML NBs), which respond to infection by accumulating at sites that are closely associated with the incoming parental HSV-1 genomes. Other cellular proteins, including IFI16, which has been implicated in sensing pathogen DNA and initiating signaling pathways that lead to an interferon response, also respond to viral genomes in this manner. Here, studies of the dynamics of the response of PML NB components and IFI16 to invading HSV-1 genomes demonstrated that this response is extremely rapid, occurring within the first hour after addition of the virus, and that human Daxx (hDaxx) and IFI16 respond more rapidly than PML. In the absence of HSV-1 regulatory protein ICP0, which counteracts the recruitment process, the newly formed, viral-genome-induced PML NB-like foci can fuse with existing PML NBs. These data are consistent with a model involving viral genome sequestration into such structures, thereby contributing to the low probability of initiation of lytic infection in the absence of ICP0.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Everett, Professor Roger
Authors: Everett, R. D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Copyright Holders:Copyright © 2016 American Society for Microbiology
First Published:First published in Journal of Virology 90(1):167-179
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656501Regulation of the initial stages of herpes simplex virus lytic infection and reactivation from latencyRoger EverettMedical Research Council (MRC)MC_UU_12014/4MVLS III - CENTRE FOR VIRUS RESEARCH
643171Medical Research Foundation Equipment Grant in Memory of Mr Alfred TartellinMassimo PalmariniMedical Research Council (MRC)C0446MVLS III - CENTRE FOR VIRUS RESEARCH