Integrating molecular archeology and Bayesian phylodynamics to elucidate the hidden history of HIV-1.

Combating pathogen spread and its associated disease burden is a tremendous challenge requiring sustained research effort and decided public health measures. The availability of genomic data provides a major asset in characterizing the interplay between viral evolution and host ecology, including the determination of the key factors for successful epidemic spread in the human population. These factors are, however, still largely unresolved for one of the most devastating pandemics in human history, the AIDS pandemic caused by Human Immunodeficiency Viruses (HIV). Despite continual developments in the field of statistical phylodynamics, historical inferences based on contemporaneous sequence data are inherently limited. Motivated by the possibility to inform such analyses with sequences recovered from archival specimens, we here propose to create a panel of ‘fossil’ HIV sequences by applying state-of-the-art sequencing technology to a unique, invaluable and comprehensive library of archival samples (n=~31.500) collected between 1955 and 1980 from different Central African locations, in particular the Democratic Republic of Congo. We will complement these efforts by advancing phylogenetic methodology to refine time-estimates for the origin of HIV-1 group M, and to reconstruct the dynamics in viral population size and spatial expansion over time. This will allow us to explicitly test different hypotheses about the emergence and early epidemic onset of HIV-1 group M.