Phylogenetic Comparison of Proposed Pathways Used b y HIV-1 Nef to Downregulate MHC-I Cell Surface Expression

Abstract

HIV-1 uses a variety of methods to avoid destruction by the host's immune system, eventually leading to AIDS. One such method is through the downregulation of major histocompatibility complex class I antigens on the infected cell's surface. Although it is known that the Nef protein is responsible, the pathway remains to be determined. Recent studies suggest two possible pathways. This study compares the pathways using phylogenetic techniques, such as the reconstruction of phylogenies of HIV-I M Group and primate immunodeficiency viruses (HIV-I, HIV-2 and SIV) for the gene, the comparison of nonsynonymous to synonymous substitutions to determine if evolution or stabilizing selection is occurring, and the determining of where in the history of the gene certain traits appear or disappear. Although this study cannot verify either pathway definitively, the pathways could be refuted by selection against essential characteristics of the pathway. Data from this study demonstrates further analysis of the endocytotic theory is necessary in the attempt to clarify the downregulation of MHC-I by HIV-I Nef. This future understanding could lead to treatment methods designed to prevent the progression of HIV-I to AIDS.