A unified evolutionary framework to reconstruct the viral histories of human, simian, and prosimian immunodeficiency viruses across timescales

The evolutionary history of simian and prosimian immunodeficiency viruses (SIVs and pSIVs) remains difficult to resolve due to time-dependent rate variation in viral evolution. Standard molecular clock methods relying on contemporary sequences often underestimate viral ages, conflicting with paleovirological and biogeographical evidence. Here, we apply the Prisoner of War model, which accounts for time-dependent rate effects, to reconstruct the evolutionary history of primate lentiviruses. Using non-recombinant genomic regions from 436 HIV, SIV, and pSIV sequences, we estimate that the most recent common ancestor of extant SIVs dates to [~]1 million years ago. The lineages giving rise to HIV-1 and HIV-2 (SIVcpz and SIVsmm) have circulated in their respective hosts for tens to hundreds of thousands of years, suggesting prolonged pre-pandemic human exposure. The divergence of SIV and pSIV is dated to 17-51 million years ago, consistent with lentiviral transfer during the last mammalian colonisation of Madagascar. Our analysis integrates lentiviral data across recent (HIV), intermediate (Bioko Island SIVs), and ancient (pSIV) timescales, enabling inferences not possible from any single timescale alone, and recovers both shallow and deep divergence events without relying on fixed internal node calibrations. This unified framework provides new insights into virus-host coevolution and zoonotic risk.