Point mutations associated with HIV-1 drug resistance, evasion of the immune response and AIDS pathogenesis

Abstract

Point mutations within the human immunodeficiency virus-type 1 (HIV-1) genome confer resistance to antiretroviral drugs. The mutations also help the virus to evade the immune system response and influence transmission and progression of the disease, collectively called acquired immune deficiency syndrome (AIDS) pathogenesis. This chapter presents an up-to-date critical review of the literature and provides a synthesis of the current understanding of HIV-1 point mutations in relation to drug resistance, evasion of the immune system and AIDS pathogenesis. First, to prime the reader, the chapter briefly describes organization and function of the HIV-1 genes. It then pinpoints salient point mutations within specific HIV-1 genes associated with resistance to current antiretroviral drugs. In particular, it pays attention to the env gene and its product, the surface envelope (Env) glycoprotein because the Env protein mediates viral entry, tropism and disease progression. Thus the role and frequencies of point mutations within the env gene is related to HIV-1 transmission dynamics and progression to AIDS. The env gene and Env protein are further unpacked to provide a better understanding of the role point mutations within this gene play in helping the virus to evade antibody mediated immune response. Finally, drawing mainly from our recent research work, the chapter proposes an aptamer-based strategy for the design of desirable approaches that can help circumvent HIV-1 point mutations and delay or diminish drug resistance.