Novel roles of focal adhesion kinase in cytoplasmic entry and replication of influenza a viruses

Husni Elbahesh, Troy Cline, Tatiana Baranovich, Elena A. Govorkova, Stacey Schultz-Cherry, Charles J. Russell

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Viruses modulate cellular signaling pathways at almost every step of the infection cycle. Cellular signaling pathways activated at later times of influenza infection have previously been investigated; however, early influenza virus-host cell interactions remain understudied. Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that regulates phosphatidylinositol 3-kinase (PI3K) activation and actin reorganization, two critical processes during influenza A virus (IAV) infection in most cell types. Using 6 influenza A virus strains (A/Puerto Rico/8/1934, A/Aichi/2/1968×A/Puerto Rico/8/1934 reassortant [X-31], A/California/04/2009, mouse-adapted A/California/04/2009, A/WSN/1933, and A/New Caledonia/20/1999), we examined the role of FAK during IAV entry. We found that influenza virus attachment induced PI3K-dependent FAK-Y397 phosphorylation. Pharmacological FAK inhibition or expression of a kinase-dead mutant of FAK led to disruption of the actin meshwork that resulted in sequestration of IAV at the cell periphery and reduced virion localization to early endosomes. Additionally, FAK inhibition impeded viral RNA replication at later times of infection and ultimately resulted in significantly reduced viral titers in both A549 and differentiated normal human bronchial epithelial (NHBE) cells. Although not all tested strains activated FAK, all of them exhibited a reduction in viral replication in response to inhibition of FAK signaling. These findings highlight novel biphasic roles of FAK activation during IAV infection and indicate that FAK serves as a central link between receptor-mediated PI3K activation and actin reorganization during IAV infection.

Original languageEnglish (US)
Pages (from-to)6714-6728
Number of pages15
JournalJournal of Virology
Volume88
Issue number12
DOIs
StatePublished - Jan 1 2014

Fingerprint

non-specific protein-tyrosine kinase
Focal Adhesion Protein-Tyrosine Kinases
Orthomyxoviridae
Influenza A virus
Phosphatidylinositol 3-Kinase
phosphatidylinositol 3-kinase
Virus Diseases
infection
actin
Actins
Puerto Rico
cell communication
phosphotransferases (kinases)
Infection
New Caledonia
Virus Attachment
Virus Internalization
endosomes
Endosomes
Viral RNA

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

Cite this

Elbahesh, H., Cline, T., Baranovich, T., Govorkova, E. A., Schultz-Cherry, S., & Russell, C. J. (2014). Novel roles of focal adhesion kinase in cytoplasmic entry and replication of influenza a viruses. Journal of Virology, 88(12), 6714-6728. https://doi.org/10.1128/JVI.00530-14

Novel roles of focal adhesion kinase in cytoplasmic entry and replication of influenza a viruses. / Elbahesh, Husni; Cline, Troy; Baranovich, Tatiana; Govorkova, Elena A.; Schultz-Cherry, Stacey; Russell, Charles J.

In: Journal of Virology, Vol. 88, No. 12, 01.01.2014, p. 6714-6728.

Research output: Contribution to journalArticle

Elbahesh, H, Cline, T, Baranovich, T, Govorkova, EA, Schultz-Cherry, S & Russell, CJ 2014, 'Novel roles of focal adhesion kinase in cytoplasmic entry and replication of influenza a viruses', Journal of Virology, vol. 88, no. 12, pp. 6714-6728. https://doi.org/10.1128/JVI.00530-14
Elbahesh H, Cline T, Baranovich T, Govorkova EA, Schultz-Cherry S, Russell CJ. Novel roles of focal adhesion kinase in cytoplasmic entry and replication of influenza a viruses. Journal of Virology. 2014 Jan 1;88(12):6714-6728. https://doi.org/10.1128/JVI.00530-14
Elbahesh, Husni ; Cline, Troy ; Baranovich, Tatiana ; Govorkova, Elena A. ; Schultz-Cherry, Stacey ; Russell, Charles J. / Novel roles of focal adhesion kinase in cytoplasmic entry and replication of influenza a viruses. In: Journal of Virology. 2014 ; Vol. 88, No. 12. pp. 6714-6728.
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