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gelsolin/severin/villin homology domain
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[viral interferon regulatory factor] This is the same as vIRF1 [viral interferon regulatory factor-1], a designation used after identification of related virus-encoded factors (vIRF2, vIRF3, vIRF4).
vIRF protein is encoded by orfK9 in the genome of KSHV [Kaposi sarcoma-associated herpesvirus] (Nicholas et al, 1997), also known as HHV-8. The gene encodes a protein with significant sequence homology to interferon regulatory factor-1, which binds to IRS (interferon response sequence) in interferon-stimulated genes. vIRF functions as a repressor for cellular interferon mediated signal transduction, and as an oncogene to induce cell growth transformation (Li et al, 1998, 2000; Gao et al, 1997; Lin et al, 2001). Li et al (2000) have demonstrated that vIRF induces global alterations of cellular gene expression by directly directly inhibiting the histone acetyltransferase activity of the cellular transcriptional coactivator p300.
Lin et al (2001) have shown that vIRF1 efficiently inhibits virus induced expression of endogenous IFN-beta, and the chemokines RANTES and IP-10 genes by selectively blocking the interferon regulatory factor IRF3.
vIRF1 binds to a transcriptional coactivator, CREB-binding protein (see: CRE, cyclic AMP-responsive element), and inhibits the transactivational activity of this binding protein in HeLa cells (Seo et al, 2000).
Choi et al (2010) have reported that vIRF1 directly targets the pro-apoptotic BCL2 family member BIM to effect its inactivation via nuclear translocation. This interaction is important to promote viral replication and to control replication-induced cell death by apoptosis.
Lagos et al (2007) have implicated vIRF1 in the regulation of antigen presentation in lymphatic endothelial cells. Lagos et al (2008) have shown that expression of the pattern recognition receptor TLR-4 is significantly downregulated upon KSHV infection. Another protein encoded by KSHV, vGPCR, contributes to suppression of TLR-4 expression as co-expression of vIRF1 and vGPCR in lymphatic endothelial cells leads to an additive effect on TLR-4 expression.
Ma et al (2007) have shown that vIRF1 disrupts interactions between GRIM-19 and the serine protease HtrAA, which augments the destruction of the anti-apoptotic protein XIAP. Disruption of these interactions confer resistance to cell death induced by interferons and retinoic acid.
Seo et al (2005) have reported that vIRF inhibits transcription and growth arrest mediated by TGF-beta by interacting with the transcriptionbal activators SMAD3 und SMAD4.
For other virus-encoded proteins with immunomodulatory/immune evasion activities and/or functions of cytokines or cytokine receptors see also the Virulence Factors Dictionary section of this encyclopedia. For other examples of microbial or parasitic gene products interfering with host cell functions see also: Modulins.
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ENTRY LAST MODIFIED: September 2011
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