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

Versteeg, G.A., Hale, B.G. , van Boheemen, S., Wolff, T., Lenschow, D.J. and García-Sastre, A. (2010) Species-specific antagonism of host ISGylation by the influenza B virus NS1 protein. Journal of Virology, 84(10), pp. 5423-5430. (doi: 10.1128/​JVI.02395-09)

Abstract

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.

• Item Type: Articles
• Keywords: Influenza
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hale, Dr Benjamin
• Authors: Versteeg, G.A., Hale, B.G., van Boheemen, S., Wolff, T., Lenschow, D.J., and García-Sastre, A.
• Subjects: Q Science > Q Science (General); Q Science > QH Natural history > QH345 Biochemistry; Q Science > QR Microbiology > QR355 Virology
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Virology
• Journal Abbr.: J. Virol.
• ISSN: 0022-538X
• ISSN (Online): 1098-5514
• Published Online: 10 March 2010