title: Influenza A virus neuraminidase protein enhances cell survival through interaction with carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) protein.
abstract: 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 of C6 resulted in a down-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.
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Road, New Delhi 110067, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Gaur
authors.forename: Priya
authors.initials: P
authors.lastname: Ranjan
authors.forename: Shipra
authors.initials: S
authors.lastname: Sharma
authors.forename: Jenish R
authors.initials: JR
authors.lastname: Patel
authors.forename: J Bradford
authors.initials: JB
authors.lastname: Bowzard
authors.forename: Shah K
authors.initials: SK
authors.lastname: Rahman
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kumari
authors.forename: Shivaprakash
authors.initials: S
authors.lastname: Gangappa
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Renu B
authors.initials: RB
authors.lastname: Lal
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Sambhara
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Lal
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D007251:Influenza, Human / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015398:Signal Transduction / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D014764:Viral Proteins; D019061:src-Family Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D009439:Neuraminidase