We have been interested in mechanisms by which cells recognizes viral infection and initiate the antiviral response. We have shown that the transcription factors of IRF and play a major role in the antiviral response and interferon induction. While viral nucleic acids can be recognized by different cellular receptors such as,. membrane associated Toll like receptors and cytoplasmic RNA helicases RIG I and MDA5 , which induce distinct signaling pathways they all lead to the activation of IRF-3, IRF-5 and IRF-7. We have shown that IRF-5 is activated by TLR7 and the human IRF-5 is expressed in multiple spliced variants of distinct transcription activity. Triple mutation in the IRF-5 gene that effects its expression and splicing was shown to be associated with predisposition to lupus. We are comparing structural and biochemical features of IRF-5 variants with their ability to stimulate antiviral and cytokine responses. In addition we are using IRF-5 and TLR7 null mice to examine their roles in immune response to viral infection, in inflammation and cancer.

Publications:

Au WC, Pitha PM. Recruitment of multiple interferon regulatory factors and histone acetyltransferase to the transcriptionally active interferon a promoters. J Biol Chem 2001; 276(45):41629-41637.

Barnes BJ, Moore PA, Pitha PM. Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes. J Biol Chem 2001; 276(26):23382-23390.

Lubyova B, Kellum MJ, Frisancho AJ, Pitha PM. Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7. J Biol Chem 2004; 279(9):7643-7654.

Atsushi A, Gengshi L, Pitha I and Pitha PM. Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein. PNAS 2006; 103(5)1440-1445

Pitha PM. Unexpected similarities in cellular responses to bacterial and viral invasion. Proc Natl Acad Sci U S A 2004; 101(3):695-696.