Type I interferons (IFNs) function as the first line of defense against viral
infections by modulating numerous biological processes to establish an antiviral state and influencing the activation of various immune cells. During influenza A infection, the NS1 encoded by the virus genome disrupts many cellular processes to block type I IFN responses. We show that expression of H5N1 NS1 in HeLa cells reduces IFN-inducible activation of STAT proteins and its subsequent binding to DNA complexes. Subsequent analysis suggests NS1 blocks IFN signaling by inhibiting expression of type I IFN receptor subunit, IFNAR1, as well as up-regulating SOCS1 expression. Finally, we demonstrate that pretreatment of primary human lung tissue with IFN alfacon-1 inhibits H5N1 viral replication by up-regulating a number of interferon-stimulated genes. The data suggest that NS1 can directly interfere with Type I IFN signaling, and that pretreatment with IFN can inhibit H5N1 infection in primary human lung tissue.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18772 |
| Date | 12 February 2010 |
| Creators | Jia, Danlin |
| Contributors | Fish, Eleanor N. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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