Paul M. Sharp
Inst. of Genetics, Univ. of Nottingham, Queens Medical Ctr., UK
It is well known that the viruses that cause AIDS (both HIV-1 and HIV-2) exhibit extremely high genetic diversity, which may be problematic for vaccine development. The historical and ongoing causes of this diversity will be examined, and their implications discussed. Comparisons will be made with other viruses for which vaccines are used successfully. A number of factors contribute to the diversity of AIDS viruses. First, HIV-1 and HIV-2 are very different because they reflect transmission into humans of two distinct lentiviruses (SIVs) from different natural host species, chimpanzees and sooty mangabeys, respectively. Second, both SIVs have been transmitted to humans on more than one occasion: for example, molecular evolutionary trees indicate that HIV-1 groups M, N, and O each reflect distinct entries into the human population of diverse examples of SIVcpz. Third, since the origin of (in particular) HIV-1 group M, the virus has diversified rapidly due to an extremely high rate of mutation and a rapid rate of replication. The current diversity of HIV-1 group M strains shows numerous discrete clades, or "subtypes." The subtypes seem to reflect different founding events during the expansion of the AIDS pandemic, but there is no simple correlation between subtypes and immunotypes. The fourth means of diversification is recombination: analyses in recent years have revealed a high frequency of viruses that are mosaics of different subtypes, implying that coinfection and/or superinfection with different strains is far from rare. Vaccines have been developed for other viruses that have mutation rates of the same order as HIV-1. For example, influenza A evolves just as fast as HIV-1. However, differences in the population biology of influenza A and HIV-1 mean that the genetic diversity of the latter is very much greater. Furthermore, although the extent of genetic diversity of influenza A is approximately stable from year to year, that of HIV-1 continues to expand. Contact Author about this Abstract
