A near full-length HIV-1 genome from 1966 recovered from formalin-fixed paraffin-embedded tissue

• DOI: 10.1073/pnas.1913682117
• Publication Date: 2020-05-19T21:20:27Z
• Authors: Sophie Gryseels; Thomas D. Watts; Jean-Marie Kabong...; Brendan B. Larsen; Philippe Lemey; Jean-Jacques Muye...; Dirk E. Teuwen; Michael Worobey
• Keywords: Adult; Male; 0301 basic medicine; 0303 health sciences; Paraffin Embedding; Time Factors; Genetic Variation; HIV Infections; Genome, Viral; Sequence Analysis, DNA; 3. Good health; Evolution, Molecular; 03 medical and health sciences; Democratic Republic of the Congo; HIV-1; Humans; Cell Lineage; Engineering sciences. Technology; Phylogeny

With very little direct biological data of HIV-1 from before the 1980s, far-reaching evolutionary and epidemiological inferences regarding the long prediscovery phase of this pandemic are based on extrapolations by phylodynamic models of HIV-1 genomic sequences gathered mostly over recent decades. Here, using a very sensitive multiplex RT-PCR assay, we screened 1,645 formalin-fixed paraffin-embedded tissue specimens collected for pathology diagnostics in Central Africa between 1958 and 1966. We report the near-complete viral genome in one HIV-1 positive specimen from Kinshasa, Democratic Republic of Congo (DRC), from 1966 (“DRC66”)—a nonrecombinant sister lineage to subtype C that constitutes the oldest HIV-1 near full-length genome recovered to date. Root-to-tip plots showed the DRC66 sequence is not an outlier as would be expected if dating estimates from more recent genomes were systematically biased; and inclusion of the DRC66 sequence in tip-dated BEAST analyses did not significantly alter root and internal node age estimates based on post-1978 HIV-1 sequences. There was larger variation in divergence time estimates among datasets that were subsamples of the available HIV-1 genomes from 1978 to 2014, showing the inherent phylogenetic stochasticity across subsets of the real HIV-1 diversity. Our phylogenetic analyses date the origin of the pandemic lineage of HIV-1 to a time period around the turn of the 20th century (1881 to 1918). In conclusion, this unique archival HIV-1 sequence provides direct genomic insight into HIV-1 in 1960s DRC, and, as an ancient-DNA calibrator, it validates our understanding of HIV-1 evolutionary history.