Species-specific antagonism of host ISGylation by the influenza B virus NS1 protein

Gijs A. Versteeg, Benjamin G. Hale, Sander Van Boheemen, Thorsten Wolff, Deborah J. Lenschow, Adolfo García-Sastre

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Interferon-stimulated expression and conjugation of the ubiquitin-like modifier ISG15 restricts replication of several viruses. Here, we established complete E1-activating, E2-conjugating, and E3 ligase-dependent expression systems for assaying both human and mouse ISGylation. We confirm that human HerC5, but not human HerC6, has ISG15 E3 ligase activity and identify mouse HerC6 as a bona fide ISG15 E3 ligase. Furthermore, we demonstrate that influenza B virus NS1 protein potently antagonizes human but not mouse ISGylation, a property dependent on B/NS1 binding the N-terminal domain of human but not mouse ISG15. Using chimeric human/mouse ISG15 constructs, we show that the B/NS1:ISG15 interaction is both necessary and sufficient to inhibit ISGylation regardless of the ligation machinery used. Inability to block ISGylation in certain species may contribute to limiting influenza B virus host range.

Original languageEnglish
Pages (from-to)5423-5430
Number of pages8
JournalJournal of Virology
Issue number10
StatePublished - May 2010


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