Influenza A virus neuraminidase protein enhances cell survival through interaction with carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) protein

Pratibha Gaur, Priya Ranjan, Shipra Sharma, Jenish R. Patel, J. Bradford Bowzard, Shah K. Rahman, Rashmi Kumari, Shivaprakash Gangappa, Jacqueline M. Katz, Nancy J. Cox, Renu B. Lal, Suryaprakash Sambhara, Sunil K. Lal

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The influenza virus neuraminidase (NA) protein primarily aids in the release of progeny virions from infected cells. Here, we demonstrate a novel role for NA in enhancing host cell survival by activating the Src/Akt signaling axis via an interaction with carcinoembryonic antigen-related cell adhesion molecule 6/cluster of differentiation 66c (C6). NA/C6 interaction leads to increased tyrosyl phosphorylation of Src, FAK, Akt, GSK3β, and Bcl-2, which affects cell survival, proliferation, migration, differentiation, and apoptosis. siRNA-mediated suppression ofC6resulted inadown-regulation of activated Src, FAK, and Akt, increased apoptosis, and reduced expression of viral proteins and viral titers in influenza virus-infected human lung adenocarcinoma epithelial and normal human bronchial epithelial cells. These findings indicate that influenza NA not only aids in the release of progeny virions, but also cell survival during viral replication.

Original languageEnglish
Pages (from-to)15109-15117
Number of pages9
JournalJournal of Biological Chemistry
Issue number18
Publication statusPublished - 27 Apr 2012
Externally publishedYes

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