Interferon Agonists/Mimetics as Therapeutics for Smallpox and Other Respiratory Viruses
Final rept. 11 Apr 2005-10 Apr 2006
FLORIDA UNIV GAINESVILLE DIV OF SPONSORED RESEARCH
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We have developed small peptide mimetics of interferon IFN gamma that bypass the receptor extracellular binding site and interact directly downstream in the IFN signaling cascade. We have synthesized these mimetics with an attached hydrophobic residue for intracellular delivery. The mimetics encompass the C-terminus of IFN gamma and unlike intact IFN gamma are species non-specific in their action. We have shown in cell culture that the IFN mimetics, like IFN, are also virus nonspecific and are highly active against the picornavirus EMC virus and the poxvirus vaccinia. Importantly, unlike IFNs that are neutralized by the decoy receptors of poxviruses, the mimetics are fully active against viruses in the presence of B8R protein that blocks IFN gamma antiviral activity. In this final report we show the progress of testing one of the IFN mimetics, IFN gamma 95-132, against lethal vaccinia virus and EMC virus infections in mice in the presence of B8R protein. We also show the mechanism of action of the IFN mimetics at the level of gene transcription.
- Medicine and Medical Research