Origins of HIV and the AIDS Epidemic

September 11-12, 2000, The Royal Society, London, United Kingdom

Jonathan Weber, FRCP, FRCPath, FmedSci, Keith Alcorn, Medical Writer

Disclosures
In This Article

When Did SIVcpz Cross the Species Barrier?

Presentations by Betty Korber of Los Alamos National Laboratory in New Mexico and Anne-Mieke Vandamme of the Rega Institute in Belgium both dated the last common ancestor for all HIV group M subtypes at around 1930. If this ancestor was a human immunodeficiency virus, this would be the very latest date at which transfer from chimps to humans might have occurred. The Rega Institute group estimates that the transfer could have occurred anywhere between 1590 and 1760, with 1675 the most likely date.

The technique used by both groups involved estimating the speed of molecular change within chosen viral genetic sequences, by comparing a variety of sequences from different dates. The Rega group removed from their calculations all sites within a sequence that did not conform to the molecular clock, a dating approach already verified in individuals with a known hepatitis C infection date in 1977. A group of Irish patients were exposed to anti-D immunoglobulin at this time, and HCV isolates from infected individuals were analyzed in 1998 in a blinded fashion to validate the technique. The group found that the more nonconforming sites they removed from the sequence, the more accurate their dating.

The Los Alamos group did not assume a stable rate of evolution, and used the earliest known HIV isolate (collected in Kinshasa in 1959) in comparison with other later isolates to verify their method. They examined the V3/V5 regions of the HIV envelope from 197 sequences gathered in Zaire in April 1997 and compared prior sequences from the same region to establish evolution rates. They established a likely date of 1940, with confidence intervals extending from 1871 to 1955.

Professor Paul Sharp's group at Nottingham University has analyzed whether there was an acceleration of genetic change in passages through new hosts, as represented by recombination events in the lineage. They hypothesized that evidence of recombination events would increase in periods where the viral subtype encountered new hosts more frequently, and that these would be detectable in the structure of the phylogenetic tree of particular subtypes. They analyzed the gag evolutionary tree and found that recent HIV-1 group M branches have a much higher ratio of changes that suggest adaptation to a new host, compared with older branches of the tree, implying that HIV-1 group M variants may have evolved slowly, sequestered in a manner similar to HIV-2, until they began to be transmitted more frequently and encountered many new hosts.

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