In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 20, No. 7 ( 2024-7-18), p. e1012256-
Abstract:
African swine fever (ASF) is a highly contagious, fatal disease of pigs caused by African swine fever virus (ASFV). The complexity of ASFV and our limited understanding of its interactions with the host have constrained the development of ASFV vaccines and antiviral strategies. To identify host factors required for ASFV replication, we developed a genome-wide CRISPR knockout (GeCKO) screen that contains 186,510 specific single guide RNAs (sgRNAs) targeting 20,580 pig genes and used genotype II ASFV to perform the GeCKO screen in wild boar lung (WSL) cells. We found that knockout of transmembrane protein 239 (TMEM239) significantly reduced ASFV replication. Further studies showed that TMEM239 interacted with the early endosomal marker Rab5A, and that TMEM239 deletion affected the co-localization of viral capsid p72 and Rab5A shortly after viral infection. An e x vivo study showed that ASFV replication was significantly reduced in TMEM239 -/- peripheral blood mononuclear cells from TMEM239 knockout piglets. Our study identifies a novel host factor required for ASFV replication by facilitating ASFV entry into early endosomes and provides insights for the development of ASF-resistant breeding.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1012256
DOI:
10.1371/journal.ppat.1012256.g001
DOI:
10.1371/journal.ppat.1012256.g002
DOI:
10.1371/journal.ppat.1012256.g003
DOI:
10.1371/journal.ppat.1012256.g004
DOI:
10.1371/journal.ppat.1012256.g005
DOI:
10.1371/journal.ppat.1012256.g006
DOI:
10.1371/journal.ppat.1012256.g007
DOI:
10.1371/journal.ppat.1012256.g008
DOI:
10.1371/journal.ppat.1012256.s001
DOI:
10.1371/journal.ppat.1012256.s002
DOI:
10.1371/journal.ppat.1012256.s003
DOI:
10.1371/journal.ppat.1012256.s004
DOI:
10.1371/journal.ppat.1012256.s005
DOI:
10.1371/journal.ppat.1012256.s006
DOI:
10.1371/journal.ppat.1012256.s007
DOI:
10.1371/journal.ppat.1012256.s008
DOI:
10.1371/journal.ppat.1012256.s009
DOI:
10.1371/journal.ppat.1012256.s010
DOI:
10.1371/journal.ppat.1012256.s011
DOI:
10.1371/journal.ppat.1012256.s012
DOI:
10.1371/journal.ppat.1012256.s013
DOI:
10.1371/journal.ppat.1012256.s014
DOI:
10.1371/journal.ppat.1012256.s015
DOI:
10.1371/journal.ppat.1012256.r001
DOI:
10.1371/journal.ppat.1012256.r002
DOI:
10.1371/journal.ppat.1012256.r003
DOI:
10.1371/journal.ppat.1012256.r004
DOI:
10.1371/journal.ppat.1012256.r005
DOI:
10.1371/journal.ppat.1012256.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2024
detail.hit.zdb_id:
2205412-1
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