Convergent Evolution of HLA-C Downmodulation in HIV-1 and HIV-2
Kristina Hopfensperger, Jonathan Richard, Christina M. Stürzel, Frédéric Bibollet‐Ruche, Richard Apps, Marie Leoz, Jean‐Christophe Plantier, Beatrice H. Hahn, Andrés Finzi, Frank Kirchhoff, Daniel Sauter
Abstract
T cell counts in HIV-infected individuals. On the one hand, efficient HLA-C expression enables the killing of infected cells by cytotoxic T lymphocytes (CTLs). On the other hand, HLA-C sends inhibitory signals to natural killer (NK) cells and enhances the infectivity of newly produced HIV particles. HIV-1 group M viruses modulate HLA-C expression using the accessory protein Vpu, possibly to balance CTL- and NK cell-mediated immune responses. Here, we show that the second human immunodeficiency virus, HIV-2, can use its accessory protein Vif to evade HLA-C-mediated restriction. Furthermore, our mutational analyses provide insights into the underlying molecular mechanisms. In summary, our results reveal how the two human AIDS viruses modulate HLA-C, a key component of the antiviral immune response.