title: Variability of HIV infections.
abstract: Genetic variation is the hallmark of infections with lentiviruses in general and the human immunodeficiency viruses (HIV-1, HIV-2) in particular. This article reviews both experimental evidence for the variability of the HIV genome during the course of an individual infection and mathematical models that outline the potential importance of antigenic variation as a major factor to drive disease progression. The essential idea is that the virus evades immune pressure by the continuous production of new mutants resistant to current immunological attack. This results in the accumulation of antigenic diversity during the asymptomatic period. The existence of an antigenic diversity threshold is derived from the asymmetric interaction between the virus quasispecies and the CD4 cell population: CD4 cells mount immune responses some of which are directed against specific HIV variants, but each virus strain can induce depletion of all CD4 cells and therefore impair immune responses regardless of their specificity. Therefore, increasing HIV diversity enables the virus population to escape from control by the immune system. In this context the observed genetic variability is responsible for the fact that the virus establishes a persistent infection without being cleared by the immune response and induces immunodeficiency disease after a long and variable incubation period. Mathematical biology has revealed a novel mechanism for viral pathogenesis.
authors.affiliation: Department of Zoology, University of Oxford, U.K.
authors.forename: M A
authors.initials: MA
authors.lastname: Nowak
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000940:Antigenic Variation / Q000235:genetics; D014644:Genetic Variation; D006678:HIV / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic