|Education||BS, University of California Irvine|
Our studies of HIV-1/HCV co-infection have involved treatment of co-infected persons with interferon-α (IFN-α), a type 1 interferon that exerts its broad antiviral effect by inducing hundreds of interferon-stimulated genes (ISG) that ultimately constrain viral replication. Using a combination of cell biological and computational approaches, we have identified several putative HIV-1 restriction factors that behave like ISG. Of the 22,227 genes detected in at least one participant, 114 genes and 20 splice variants were significantly changed (P corrected<0.05) by IFN treatment. We identified 5 genes with induction dynamics that non-randomly associate with control of HIV including MX2, a gene described as having some antiviral activity against HIV in vitro (Kane et al, Nature 2013). Our current efforts are focused on understanding the antiviral mechanisms underlying LAMP3, BCL-G, and CMPK2 putative HIV-1 restriction factors in vitro, and to link their activity to IFN-α induction. After identifying HIV-1 restriction factors, we will extend our findings to test where they inhibit the HIV-1 life cycle and whether our newly identified ISGs also restrict replication of other viruses (Influenza, HCV, Sendai).