Abstract
The evolutionary history of simian and prosimian immunodeficiency viruses (SIVs and pSIVs) remains difficult to resolve, because divergence-time estimates from standard clock analyses using contemporary sequences conflict with palaeovirological and biogeographical evidence. One proposed explanation is that inferred substitution rates decline with increasing timescale, a pattern known as the time-dependent rate phenomenon. Here, we apply the Prisoner of War model, which maps genetic divergence to time under a mechanistic model of time-dependent rate decay, to reconstruct the evolutionary history of primate lentiviruses. Using non-recombinant genomic regions from 436 human immunodeficiency virus (HIV), SIV and pSIV sequences, we estimate that the most recent common ancestor of extant SIVs dates to approximately 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 between the lineages leading to extant SIV and Malagasy pSIV is dated to 17-51 million years ago, consistent with ancient lentiviral transfer via over-water dispersal and/or non-primate vectors. Our analysis reconciles divergence-time estimates of primate lentiviruses across recent (HIV), intermediate (Bioko Island SIVs) and ancient (pSIV) timescales under an explicit model of time-dependent rate decay, enabling inferences not possible from any single timescale alone. It also highlights the sensitivity of deep viral dating to modelling assumptions, recombination and locus-specific evolutionary histories. This model-based framework provides new insights into primate lentivirus origins, virus-host associations and zoonotic risk.