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J. Virol. doi:10.1128/JVI.00985-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Unequal evolutionary rates in the HIV-1 pandemic: The evolutionary rate of HIV-1 slows down when the epidemic rate increases

Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden, Theoretical Biology and Biophysics, T-10, MS K710, Los Alamos National Laboratory, Los Alamos, NM, 87545 USA

^* To whom correspondence should be addressed. Email: inam{at}lanl.gov.

	Abstract

HIV-1 sequences in intravenous drug user (IDU) networks are highly homogenous even after several years, while this is not observed in most sexual epidemics. To address this disparity, we examined the HIV-1 evolutionary rate on the population level in IDU and heterosexual transmissions. All available HIV-1 env V3 sequences from IDU outbreaks and heterosexual epidemics with known sampling dates were collected from the Los Alamos HIV sequence database. Evolutionary rates were calculated using phylogenetic trees with a T-test root optimization of dated samples. The evolutionary rate of HIV-1 subtype A1 was found to be 8.4 times slower in fast spread among IDUs in the Former Soviet Union (FSU) than in slow spread among heterosexual individuals in Africa. Mixed epidemics (IDU and heterosexual) showed intermediate evolutionary rates, indicating a combination of fast and slow spread patterns. Hence, if transmissions occur repeatedly during the initial stage of host infection, before selective pressures of the immune system have much impact, the rate of the HIV-1 evolution on the population level will decrease. Conversely, in slow spread, where HIV-1 evolves under the pressure of the immune system before a donor infects a recipient, the virus evolution at the population level will increase. Epidemiological modeling confirmed that the evolutionary rate of HIV-1 depends on the rate of spread, and predicted that the HIV-1 evolutionary rate in a fast spreading epidemic, e.g., IDU-FSU, will increase as the population becomes saturated with infections and the virus starts to spread to other risk groups.

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• Holmes, E. C. (2007). When HIV spread afar. Proc. Natl. Acad. Sci. USA 104: 18351-18352 [Full Text]