title: Inhibition of vesicular stomatitis virus infection in epithelial cells by alpha interferon-induced soluble secreted proteins.
abstract: Interferons (IFNs) are potent antiviral cytokines that inhibit infection by a wide spectrum of viruses by activating the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. Several IFN-induced antiviral proteins including 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and Mx play a critical role in conferring the antiviral properties of IFN. However, studies have shown that additional antiviral factors are involved in addition to these proteins during IFN-mediated antiviral action. In an effort to characterize these novel antiviral factors, the antiviral mechanism of alpha IFN (IFN-alpha) against vesicular stomatitis virus (VSV) was investigated in human lung epithelial A549 cells. These studies demonstrated that soluble secreted antiviral proteins as the constituents of conditioned medium prepared from IFN-alpha-treated cells reduced VSV infectivity by more than 2 logs, compared with a 4 log inhibition observed following treatment of cells with IFN-alpha. The antiviral mechanism of these secreted proteins appeared to act at the level of cellular entry of VSV. Interestingly, the IFN-alpha-induced antiviral proteins were secreted independently of STAT1 (an essential component of the JAK/STAT pathway), demonstrating that the release of such extracellular soluble antiviral proteins from cells may represent an alternative mechanism of the antiviral defence strategy of IFN towards VSV infection.
authors.affiliation: Department of Molecular Genetics/Virology Section, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Mausumi
authors.initials: M
authors.lastname: Basu
authors.affiliation: Virus Core Facility, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Ratan K
authors.initials: RK
authors.lastname: Maitra
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, MC 7758, San Antonio, TX 78229-3900, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, MC 7758, San Antonio, TX 78229-3900, USA.
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Molecular Genetics/Virology Section, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Amiya K
authors.initials: AK
authors.lastname: Banerjee
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, MC 7758, San Antonio, TX 78229-3900, USA.
authors.forename: Santanu
authors.initials: S
authors.lastname: Bose
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D002460:Cell Line; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D014176:Protein Biosynthesis; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D012995:Solubility; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000998:Antiviral Agents; D017077:Culture Media, Conditioned; D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human