EVOLUTIONARY BIOLOGY OF HUMAN-IMMUNODEFICIENCY-VIRUS

The human immunodeficiency viruses, HIV-1 and HIV-2, are members of a group of closely related viruses found in a number of different African primate species. More distantly related lentiviruses are found in several different mammalian orders. All are associated with long-term infections, but the outcome of infection ranges from a complete absence of symptoms to a rapidly developing immunodeficiency and death. While HIV-2 is probably directly related to a virus that is responsible for an asymptomatic infection in the Sooty Mangabey, no obvious candidate for the progenitor of HIV-1 has yet been found. Substantial genetic diversity is present in all immunodeficiency viruses, and phylogenetic analysis of HIV-1 sequences obtained from a wide range of geographic locations has revealed 5-7 groups of viral strains, all equally distant from each other. All groups have been found in Africa, but their distribution elsewhere reflects chance links between individuals at high risk of infection. In some areas large epidemics have spread through groups of such individuals to infect thousands within a few months, resulting in an increase in the global frequency of the particular strain responsible, without the occurrence of any significant diversification. In contrast, within infected patients, substantial diversity is developed over the period of the infection, especially in regions of the envelope gene which are targets for immune recognition (frequency-dependent selection). However, this diversity appears to be reduced at transmission (stabilizing selection). Analysis of these different evolutionary forces gives insights into the development of drug resistance and to potentially protective immune responses which are of practical value, while providing novel observations on molecular evolution in real time.