title: The vesicular stomatitis virus matrix protein inhibits NF-κB activation in mouse L929 cells.
abstract: A previous study found that NF-κB activation is delayed in L929 cells infected with wild-type (wt) strains of VSV, while activation occurred earlier in cells infected with mutant strain T1026R1 (R1) that encodes a mutation in the cytotoxic matrix (M) protein. The integrity of the other R1 proteins is unknown; therefore our goal was to identify the viral component responsible for preventing NF-κB activation in L929 cells. We found that the M protein inhibits viral-mediated activation of NF-κB in the context of viral infection and when expressed alone via transfection, and that the M51R mutation in M abrogates this function. Addition of an IκB kinase (IKK) inhibitor blocked NF-κB activation and interferon-β mRNA expression in cells infected with viruses encoding the M51R mutation in M. These results indicate that the VSV M protein inhibits activation of NF-κB by targeting an event upstream of IKK in the canonical pathway.
authors.affiliation: Thomas Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, New York, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Varble
authors.affiliation: Thomas Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, New York, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Ried
authors.affiliation: Thomas Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, New York, USA.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Hammond
authors.affiliation: Thomas Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, New York, USA.
authors.forename: Kaitlin A
authors.initials: KA
authors.lastname: Marquis
authors.affiliation: Thomas Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, New York, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Woodruff
authors.affiliation: Thomas Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, New York, USA. Electronic address: mcfsbi@rit.edu.
authors.forename: Maureen C
authors.initials: MC
authors.lastname: Ferran
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression; D051550:I-kappa B Kinase / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding; D054243:Vesicular Stomatitis / Q000235:genetics / Q000378:metabolism / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C094460:M protein, Vesicular stomatitis virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D016899:Interferon-beta; D051550:I-kappa B Kinase
keywords: Canonical pathway; IKK inhibitor; Interferon; L929 cells; M51 mutation; Matrix protein; NF-kappa B (NF-κB); VSV; Vesicular stomatitis virus