Dating HIV and HCV epidemics with a new method to uncover clock-like molecular evolution: HIV-1 group M orginated during the 1930s.
Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA163)
Vandamme A-M, Salemi M, Stirmmer K, Hall W, Duffy M, Delaporte E, Mboup S, Peeters M A.-M. Vandamme, Rega Institute, Minderbroedersstraat 10, 3000 Leuven, Belgium, Tel.: +32 16 33 21 60, Fax: +32 16 33 21 31, E-mail: annemie.vandamme@uz.kuleuven.ac.be
In principle, the time of origin of the most recent common ancestor for a clade of contemporary virus strains can be estimated from a phylogenetic tree provided the molecular clock hypothesis holds. However, it has been shown that viruses like HIV and HCV do not follow a molecular clock because of the unequal evolutionary rates among different viral lineages and different subtypes. In order to date the common ancestor of viral strains evolving at different rates, we developed a new method, called Site Stripping for Clock Detection (SSCD). This method allows selection of nucleotide sites evolving at an equal rate in the different lineages, thus extracting the clock-like information. The method was applied on a dataset of patients all infected with HCV in 1977 by the same donor. The evolutionary rate of the clock-like sites for HCV was calculated taking comparing strains from the infected recipients isolated in 1994 and in 1998. Using the SSCD method and the calibrated evolutionary rate for the stripped alignment, we were able to date exactly the "known" origin of the infection. We used the same method on two different HIV datasets, one in the pol region dating from 1998, and one in the env region dating from 1992, and calibrated the clock using all pol and env isolates respectively, reported in the database with a known isolation date. Both datasets gave us a compatible date for the origin of HIV-1 group M radiation, which was during the 1930s. Similarly, the separation of HIV-1 and its currently closest simian counterpart occurred around 1800 AD. These results shed new light on the origin of the AIDS pandemic and seem to dismiss hypotheses of a more recent origin for HIV-1 group M such as proposing that humans became infected as a result of vaccination with Oral Polio Vaccine batches contaminated with SIV. SSCD appears to be an easy to use and generally applicable method to uncover clock-like evolving sites in a set of aligned sequences.
Keywords: AEGIS, HIV-1, Evolution, Molecular, HIV Infections, HIV Seropositivity, SIV, Disease Outbreaks, Acquired Immunodeficiency Syndrome, Hepacivirus, Human, Epidemiology, genetics, methods 000709
MoOrA163