title: Caspase-mediated degradation of host cortactin that promotes influenza A virus infection in epithelial cells.
abstract: Influenza A virus (IAV) is well-known to exploit host factors to its advantage. Here, we report that IAV exploits host cortactin, an actin filament-stabilising protein for infection in epithelial cells. By using RNA interference-mediated knockdown and overexpression approach, we demonstrate that cortactin promotes IAV infection. However, cortactin polypeptide undergoes the degradation during late IAV infection. By perturbing the lysosome and proteasome, two main compartments governing the degradation of mammalian proteins, we demonstrate that a lysosome-associated apoptotic pathway mediates the degradation of cortactin in IAV-infected cells. However, we could not detect cleaved cortactin fragments by western blotting using the antibodies recognising either N-terminal/Central or C-terminal cortactin regions, which suggested the presence of multiple caspase cleavage sites. Indeed, CaspDB, a recently-described database predicted up to 35 caspase cleavage motifs present across cortactin polypeptide. The data presented indicate that host cortactin potentially has a dual but contrasting role during IAV infection.
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: Da-Yuan
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand. Electronic address: matloob.husain@otago.ac.nz.
authors.forename: Matloob
authors.initials: M
authors.lastname: Husain
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism / Q000821:virology; D008247:Lysosomes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis
chemical_list: D000199:Actins; D051356:Cortactin; D010455:Peptides; D053148:Caspase 3; D020169:Caspases
keywords: Actin-binding protein; Actin-stabilising protein; Caspase; Cortactin; Influenza A virus; Lysosomal degradation