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Effects of Nonstructural Proteins (NS) of Respiratory Syncytial Virus (RSV) on Host Interferon Response
Author(s) -
Swedan Samer Fuad,
Barik Sailen
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.524.6
Subject(s) - stat2 , biology , interferon , paramyxoviridae , virology , virus , viral replication , pneumovirus , pneumovirinae , mononegavirales , gene , genetics , stat , viral disease , stat3
RSV is a Pneumovirus of the Paramyxoviridae family. To replicate efficiently, RSV interacts with the host cell to inhibit cellular innate immunity. RSV has two nonstructural proteins, NS1 and NS2, which have no homology with any other gene in biology. Both are dispensable for RSV replication in cell culture, but needed for robust virus infection in animals. Both NS proteins have interferon (IFN) antagonist activity. The project's goal is to define the functions of the NS1 and NS2 proteins of RSV in viral replication and pathogenesis. More specifically, the amino acid residues of the NS proteins essential for IFN antagonism will be identified and host proteins that interact with the NS proteins will be determined. The central hypothesis is that NS1 and NS2 antagonize IFN production by interacting with components of IFN induction and response cascades. To test this hypothesis, techniques such as site‐directed mutagenesis of NS genes, luciferase reporter assays, and IFN functional assays will be employed. This will provide an integrated view of the structural determinants of NS proteins on IFN antagonism and the effects of altering these determinants on RSV biology. Initial results indicate that NS1 and NS2 prevent the induction of IFN‐β and implicate the ten c‐terminal residues of NS2 in the degradation of STAT2. Research sponsored by Alabama EPSCoR and NIH Grant AI059267