HIV: Biochemistry and Pathogenicity
Since the Human Immunodeficiency Virus (HIV) was discovered in 1983 by Francoise BarrÃ¨-Sinoussi and colleagues (reviewed by Weiss, 2013) an estimated 70 million people have been infected with this retrovirus (WHO, 2013). Of these, close to half have died of the clinical manifestation of the infection called AIDS (Acquired Immune Deficiency Syndrome). Although tremendous progress has been made, including accurate testing of patients and donated blood, development of effective anti-retroviral therapy (ART) drugs, and viral load testing to track patient progress, the antigenic diversity of the viral coat has stymied the development of an effective vaccine (reviewed by Weiss, 2013).
HIV-1 Viral Coat Proteins
The HIV-1 diploid RNA genome is encapsulated in a lipid bilayer studded on the exterior surface with glycoproteins (reviewed by Weiss, 2013). These glycoproteins are composed a trimeric structure of three transmembrane proteins (gp41) bound to a trimeric surface glycoprotein (gp120), which together are called the envelope protein (ENV). GP120 is highly glycosylated and forms a protective glycan shield around the viral envelope. Both gp120 and gp41 can participate in binding to the CD4 epitope on the surface of T-helper cells and macrophages, thereby initiating HIV-1 infection of critical immune cells. However, progression to the point of fusing the viral lipid bilayer with the cytoplasmic membrane of CD4+ cells requires the added