The Wilson Group
My group focuses on identifying and characterising novel interferon stimulated genes (ISGs) that protect cells from viral infection. Using ISG-expression libraries we study a diverse range of retroviruses where multiple ISGs have redefined our understanding of species-specific restriction.
Mx2 and HIV-1
Even though the human repertoire of antiviral defences doesn't prevent or clear HIV-1 infection, we are interested in how our ISGs might interfere with HIV-1 replication. Crucially, interferon-treated patients have lower HIV-1 viral loads indicating that our human interferon response has the potential to attenuate HIV-1. Recently, several groups independently identified the ISG Mx2/MxB as being able to inhibit the early events of HIV-1 infection. We were interested in how Mx2 might inhibit HIV-1. To this end, we investigated the ability of species variants of Mx2 to inhibit HIV-1. Interestingly we found that anti-HIV-1 activity seemed restricted to primates with dog and sheep variants of Mx2 unable to inhibit infection. We used this observation to demonstrate that the antiviral activity of Mx2 was specified by the N-terminus of the protein. Remarkably, by grafting 29 residues from the N-terminus of human Mx2 onto dog Mx2 we generated a chimeric antiviral protein, indicating that antiviral specificity determinant(s) reside in this region.