Genetic variability
HIV differs from many viruses in that it has very high genetic variability. This diversity is a result of its fast replication cycle, with the generation of about 1010 virions every day, coupled with a high mutation rate of approximately 3 x 10−5 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase.[101][102][103]
This complex scenario leads to the generation of many variants of HIV in a single infected patient in the course of one day.[101] This variability is compounded when a single cell is simultaneously infected by two or more different strains of HIV. When simultaneous infection occurs, the genome of progeny virions may be composed of RNA strands from two different strains. This hybrid virion then infects a new cell where it undergoes replication. As this happens, the reverse transcriptase, by jumping back and forth between the two different RNA templates, will generate a newly synthesized retroviral DNA sequence that is a recombinant between the two parental genomes.[101] This recombination is most obvious when it occurs between subtypes.[101]
The closely related simian immunodeficiency virus (SIV) has evolved into many strains, classified by the natural host species. SIV strains of the African green monkey (SIVagm) and sooty mangabey (SIVsmm) are thought to have a long evolutionary history with their hosts. These hosts have adapted to the presence of the virus,[104] which is present at high levels in the host's blood but evokes only a mild immune response,[105] does not cause the development of simian AIDS,[106] and does not undergo the extensive mutation and recombination typical of HIV infection in humans.[107]
In contrast, when these strains infect species that have not adapted to SIV ("heterologous" hosts such as rhesus or cynomologus macaques), the animals develop AIDS and the virus generates genetic diversity similar to what is seen in human HIV infection.[108] Chimpanzee SIV (SIVcpz), the closest genetic relative of HIV-1, is associated with increased mortality and AIDS-like symptoms in its natural host.[109] Both SIVcpz and HIV-1 appear to have been transmitted relatively recently to chimpanzee and human populations, so their hosts have not yet adapted to the virus.[104] Both viruses have also lost a function of the Nef gene that is present in most SIVs; without this function, T cell depletion is more likely, leading to immunodeficiency.[109]
Three groups of HIV-1 have been identified on the basis of differences in the envelope (env) region: M, N, and O.[110] Group M is the most prevalent and is subdivided into eight subtypes (or clades), based on the whole genome, which are geographically distinct.[111] The most prevalent are subtypes B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes form branches in the phylogenetic tree representing the lineage of the M group of HIV-1. Coinfection with distinct subtypes gives rise to circulating recombinant forms (CRFs). In 2000, the last year in which an analysis of global subtype prevalence was made, 47.2% of infections worldwide were of subtype C, 26.7% were of subtype A/CRF02_AG, 12.3% were of subtype B, 5.3% were of subtype D, 3.2% were of CRF_AE, and the remaining 5.3% were composed of other subtypes and CRFs.[112] Most HIV-1 research is focused on subtype B; few laboratories focus on the other subtypes.[113] The existence of a fourth group, "P", has been hypothesised based on a virus isolated in 2009.[114][115][116] The strain is apparently derived from gorilla SIV (SIVgor), first isolated from western lowland gorillas in 2006.[114]
The genetic sequence of HIV-2 is only partially homologous to HIV-1 and more closely resembles that of SIVsmm
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