In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 2 ( 2021-2-11), p. e1009336-
Abstract:
Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009336
DOI:
10.1371/journal.ppat.1009336.g001
DOI:
10.1371/journal.ppat.1009336.g002
DOI:
10.1371/journal.ppat.1009336.g003
DOI:
10.1371/journal.ppat.1009336.g004
DOI:
10.1371/journal.ppat.1009336.g005
DOI:
10.1371/journal.ppat.1009336.g006
DOI:
10.1371/journal.ppat.1009336.g007
DOI:
10.1371/journal.ppat.1009336.g008
DOI:
10.1371/journal.ppat.1009336.g009
DOI:
10.1371/journal.ppat.1009336.g010
DOI:
10.1371/journal.ppat.1009336.s001
DOI:
10.1371/journal.ppat.1009336.s002
DOI:
10.1371/journal.ppat.1009336.s003
DOI:
10.1371/journal.ppat.1009336.s004
DOI:
10.1371/journal.ppat.1009336.s005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
