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Viruses 2016, 8(4), 101;

Nuclear Translocation of Crk Adaptor Proteins by the Influenza A Virus NS1 Protein

Department of Virology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland
Department of Virology, University of Turku, 20520 Turku, Finland and Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), 00300 Helsinki, Finland
Author to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 9 February 2016 / Revised: 31 March 2016 / Accepted: 4 April 2016 / Published: 15 April 2016
(This article belongs to the Section Animal Viruses)
Full-Text   |   PDF [1979 KB, uploaded 15 April 2016]   |  


The non-structural protein-1 (NS1) of many influenza A strains, especially those of avian origin, contains an SH3 ligand motif, which binds tightly to the cellular adaptor proteins Crk (Chicken tumor virus number 10 (CT10) regulator of kinase) and Crk-like adapter protein (CrkL). This interaction has been shown to potentiate NS1-induced activation of the phosphatidylinositol 3-kinase (PI3K), but additional effects on the host cell physiology may exist. Here we show that NS1 can induce an efficient translocation of Crk proteins from the cytoplasm into the nucleus, which results in an altered pattern of nuclear protein tyrosine phosphorylation. This was not observed using NS1 proteins deficient in SH3 binding or engineered to be exclusively cytoplasmic, indicating a physical role for NS1 as a carrier in the nuclear translocation of Crk. These data further emphasize the role of Crk proteins as host cell interaction partners of NS1, and highlight the potential for host cell manipulation gained by a viral protein simply via acquiring a short SH3 binding motif. View Full-Text
Keywords: NS1; influenza A virus; SH3 domain; Crk; virus-host interaction NS1; influenza A virus; SH3 domain; Crk; virus-host interaction

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Ylösmäki, L.; Fagerlund, R.; Kuisma, I.; Julkunen, I.; Saksela, K. Nuclear Translocation of Crk Adaptor Proteins by the Influenza A Virus NS1 Protein. Viruses 2016, 8, 101.

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