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The switch between acute and persistent paramyxovirus infection caused by single amino acid substitutions in the RNA polymerase P subunit

Young, DF; Wignall-Fleming, EB; Busse, DC; Pickin, MJ; Hankinson, J; Randall, EM; Tavendale, A; Davison, AJ; Lamont, D; Tregoning, JS; et al. Young, DF; Wignall-Fleming, EB; Busse, DC; Pickin, MJ; Hankinson, J; Randall, EM; Tavendale, A; Davison, AJ; Lamont, D; Tregoning, JS; Goodbourn, S; Randall, RE (2019) The switch between acute and persistent paramyxovirus infection caused by single amino acid substitutions in the RNA polymerase P subunit. PLoS Pathog, 15 (2). e1007561. ISSN 1553-7374 https://doi.org/10.1371/journal.ppat.1007561
SGUL Authors: Goodbourn, Stephen Edward

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Abstract

Paramyxoviruses can establish persistent infections both in vitro and in vivo, some of which lead to chronic disease. However, little is known about the molecular events that contribute to the establishment of persistent infections by RNA viruses. Using parainfluenza virus type 5 (PIV5) as a model we show that phosphorylation of the P protein, which is a key component of the viral RNA polymerase complex, determines whether or not viral transcription and replication becomes repressed at late times after infection. If the virus becomes repressed, persistence is established, but if not, the infected cells die. We found that single amino acid changes at various positions within the P protein switched the infection phenotype from lytic to persistent. Lytic variants replicated to higher titres in mice than persistent variants and caused greater infiltration of immune cells into infected lungs but were cleared more rapidly. We propose that during the acute phases of viral infection in vivo, lytic variants of PIV5 will be selected but, as the adaptive immune response develops, variants in which viral replication can be repressed will be selected, leading to the establishment of prolonged, persistent infections. We suggest that similar selection processes may operate for other RNA viruses.

Item Type: Article
Additional Information: © 2019 Young et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: 0605 Microbiology, 1107 Immunology, 1108 Medical Microbiology, Virology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLoS Pathog
ISSN: 1553-7374
Language: eng
Dates:
DateEvent
11 February 2019Published
4 January 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
101792/Z/13/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
101788/Z/13/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
109056/Z/15/AWellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_UU_12014/3Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0801822Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
109056/Z/15/AWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 30742688
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/110523
Publisher's version: https://doi.org/10.1371/journal.ppat.1007561

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