Open AccessNonproteolytic K29-Linked Ubiquitination of the PB2 Replication Protein of Influenza A Viruses by Proviral Cullin 4-Based E3 Ligases
Author(s) -
Marwah Karim,
Élise Biquand,
Marion Declercq,
Yves Jacob,
Sylvie van der Werf,
Caroline Demeret
Publication year - 2020
Publication title -
mbio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.562
H-Index - 121
eISSN - 2161-2129
pISSN - 2150-7511
DOI - 10.1128/mbio.00305-20
Subject(s) - ubiquitin , cullin , biology , viral replication , virology , virus , ubiquitin ligase , influenza a virus , microbiology and biotechnology , gene , genetics
Successful infection by influenza A virus, a pathogen of major public health importance, involves fine regulation of the multiple functions of the viral proteins, which often relies on post-translational modifications (PTMs). The PB2 protein of influenza A viruses is essential for viral replication and a key determinant of host range. While PTMs of PB2 inducing its degradation have been identified, here we show that PB2 undergoes a regulating PTM signaling detected during infection, based on an atypical K29-linked ubiquitination and mediated by two multicomponent E3 ubiquitin ligases. Recombinant viruses impaired for CRL4-mediated ubiquitination are attenuated, indicating that ubiquitination of PB2 is necessary for an optimal influenza A virus infection. The CRL4 E3 ligases are required for normal viral cycle progression and for maximal virion production. Consequently, they represent potential candidate host factors for antiviral targets.