Jean-Baptiste Gorin , Markus Moll , Louisa Zimmermann  , Edwin Leeansyah, Johan K. Sandberg 
Affiliates:  Centre for Infectious Medicine (CIM), department of Medicine Huddinge
Many viruses encode proteins that have the capacity to interfere with host antigen presentation. The HIV-1 Vpu and Nef accessory proteins are known to interfere with cell surface expression of both classical (HLA) and non-classical (CD1d) MHC proteins, resulting in reduced recognition of infected cells by T cells and invariant natural killer T (iNKT) cells, respectively. Recently, others and we have shown that mucosal associated invariant T (MAIT) cells are numerically and functionally impaired in chronically infected HIV-1 patients. These cells recognise bacterial riboflavin metabolite antigens presented on the MHC class-I related (MR1) protein, and thus provide an evolutionarily conserved system for recognition of a broad range of microbes. In this study, we investigate the effects of HIV-1 Vpu and Nef proteins on MR1 expression. Our findings indicate that these viral proteins both act to decrease the cell surface expression of MR1. By using various mutants of the Vpu protein, we also show that the trans-membrane domain of Vpu is important for this effect while the highly conserved DSGxxS motif in the hinge region, which allows the recruitment of the ubiquitin ligase complex, does not seem to be required. These findings indicate that the HIV-1 Nef and Vpu proteins together act to interfere with MR1 antigen presentation. This may have implications for the ability of MAIT cells to function in HIV-1 infected patients.