Heikkinen, Leena S. and Kazlauskas, Arunas and Melen, Krister and Wagner, Ralf and Ziegler, Thedi and Julkunen, Ilkka and Saksela, Kalle (2008) Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL src homology 3 domains to activate host cell signaling. JOURNAL OF BIOLOGICAL CHEMISTRY, 283 (9). pp. 5719-5727. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
NS1 (nonstructural protein 1) is an important virulence factor of the influenza A virus. We observed that NS1 proteins of the 1918 pandemic virus (A/ Brevig Mission/ 1/ 18) and many avian influenza A viruses contain a consensus Src homology 3 (SH3) domain-binding motif. Screening of a comprehensive human SH3 phage library revealed the N-terminal SH3 of Crk and CrkL as the preferred binding partners. Studies with recombinant proteins confirmed avid binding of NS1 proteins of the 1918 virus and a representative avian H7N3 strain to Crk/ CrkL SH3 but not to other SH3 domains tested, including p85 alpha and p85 beta. Endogenous CrkL readily co-precipitated NS1 from cells infected with the H7N3 virus. In transfected cells association with CrkL was observed for NS1 of the 1918 and H7N3 viruses but not A/ Udorn/ 72 or A/WSN/ 33 NS1 lacking this sequence motif. SH3 binding was dispensable for suppression of interferoninduced gene expression by NS1 but was associated with enhanced phosphatidylinositol 3-kinase signaling, as evidenced by increased Akt phosphorylation. Thus, the Spanish Flu virus resembles avian influenza A viruses in its ability to recruit Crk/CrkL to modulate host cell signaling.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PRE-MESSENGER-RNAS; ADAPTER PROTEIN; SH3 DOMAINS; 3-KINASE/AKT PATHWAY; ANTIVIRAL RESPONSES; PANDEMIC INFLUENZA; PHAGE-DISPLAY; SPECIFICITY; INTERFERON; SEQUENCE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Nov 2020 09:58 |
| Last Modified: | 09 Nov 2020 09:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31361 |
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