Dating the Age of the SIV Lineages That Gave Rise to HIV-1 and HIV-2

Abstract

Great strides have been made in understanding the evolutionary history of simian immunodeficiency virus (SIV) and the zoonoses that gave rise to HIV-1 and HIV-2. What remains unknown is how long these SIVs had been circulating in non-human primates before the transmissions to humans. Here, we use relaxed molecular clock dating techniques to estimate the time of most recent common ancestor for the SIVs infecting chimpanzees and sooty mangabeys, the reservoirs of HIV-1 and HIV-2, respectively. The date of the most recent common ancestor of SIV in chimpanzees is estimated to be 1492 (1266–1685), and the date in sooty mangabeys is estimated to be 1809 (1729–1875). Notably, we demonstrate that SIV sequences sampled from sooty mangabeys possess sufficient clock-like signal to calibrate a molecular clock; despite the differences in host biology and viral dynamics, the rate of evolution of SIV in sooty mangabeys is indistinguishable from that of its human counterpart, HIV-2. We also estimate the ages of the HIV-2 human-to-human transmissible lineages and provide the first age estimate for HIV-1 group N at 1963 (1948–1977). Comparisons between the SIV most recent common ancestor dates and those of the HIV lineages suggest a difference on the order of only hundreds of years. Our results suggest either that SIV is a surprisingly young lentiviral lineage or that SIV and, perhaps, HIV dating estimates are seriously compromised by unaccounted-for biases.

Author Summary

HIV/AIDS continues to be a major health problem worldwide. An understanding of the evolution of HIV in humans may be greatly improved by detailed knowledge of its predecessor, simian immunodeficiency virus (SIV), in non-human primates. While HIV causes AIDS in humans, SIV generally produces a benign infection in its natural hosts. This avirulence is often attributed to coevolution between the virus and its host, possibly due to codivergence over millions of years. Here, we provide a temporal reference for evolution of SIV in its natural primate hosts. Using state-of-the-art molecular clock dating techniques, we estimate the time of most recent common ancestor for SIV in sooty mangabeys and chimpanzees at 1809 (1729–1875) and 1492 (1266–1685), respectively. These ages indicate that SIV may have infected these natural hosts for only hundreds of years before giving rise to HIV. This short duration suggests that viral–host coevolution over millions of years is not a likely explanation for the widespread avirulence of SIV. Finally, despite differences between SIV and HIV in host biology and viral pathogenicity, we have found clear and direct evidence that SIV evolves at a rapid rate in its natural hosts, an evolutionary rate that is indistinguishable from that of HIV in humans.