Altmetric

ANP32 proteins are essential for influenza virus replication in human cells

File Description SizeFormat 
Journal of Virology-2019-Staller-JVI.00217-19.full.pdfAccepted version2.39 MBAdobe PDFView/Open
Title: ANP32 proteins are essential for influenza virus replication in human cells
Authors: Staller, E
Sheppard, CM
Neasham, PJ
Mistry, B
Peacock, TP
Goldhill, DH
Long, JS
Barclay, WS
Item Type: Journal Article
Abstract: ANP32 proteins have been implicated in supporting influenza virus replication, but most of the work to date has focused on the ability of avian Anp32 proteins to overcome restriction of avian influenza polymerases in human cells. Using a CRISPR approach we show that human ANP32A and ANP32B are functionally redundant but essential host factors for mammalian-adapted influenza A virus (IAV) and influenza B virus (IBV) replication in human cells. When both proteins are absent from human cells, influenza polymerases are unable to replicate the viral genome, and infectious virus cannot propagate. Provision of exogenous ANP32A or –B recovers polymerase activity and virus growth. We demonstrate that this redundancy is absent in the murine Anp32 orthologues: murine Anp32A is incapable of recovering IAV polymerase activity, while murine Anp32B can. Intriguingly, IBV polymerase is able to use murine Anp32A. We show using a domain swap and point mutations that the LRR 5 region comprises an important functional domain for mammalian ANP32 proteins. Our approach has identified a pair of essential host factors for influenza virus replication and can be harnessed to inform future interventions.
Issue Date: 13-Aug-2019
Date of Acceptance: 1-Jun-2019
URI: http://hdl.handle.net/10044/1/70985
DOI: 10.1128/jvi.00217-19
ISSN: 0022-538X
Publisher: American Society for Microbiology
Journal / Book Title: Journal of Virology
Volume: 93
Issue: 17
Copyright Statement: © 2019 Staller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Wellcome Trust
Funder's Grant Number: BB/K002465/1
105396/Z/14/Z
205100/Z/16/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
ANP32
ANP32A
ANP32B
CRISPR
host factor
influenza
polymerase
replication
virus
RNA-SYNTHESIS
TRANSCRIPTION
INSIGHTS
SCREEN
ACETYLATION
CRISPR/CAS9
MORTALITY
APOPTOSIS
PLATFORM
COMPLEX
ANP32
ANP32A
ANP32B
CRISPR
host factor
influenza
polymerase
replication
virus
06 Biological Sciences
07 Agricultural and Veterinary Sciences
11 Medical and Health Sciences
Virology
Publication Status: Published
Article Number: e00217-19
Online Publication Date: 2019-06-19
Appears in Collections:Department of Medicine
Faculty of Medicine



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons