article · Proceedings of the National Academy of Sciences
Using a sensitive multiplex RT-PCR assay, a screening of 1,645 archival formalin-fixed paraffin-embedded tissue samples collected in Central Africa between 1958 and 1966 identified a near-complete HIV-1 viral genome from Kinshasa, Democratic Republic of Congo, dating from 1966. Designated as DRC66, this sequence represents the oldest near full-length HIV-1 genome recovered to date and forms a non-recombinant sister lineage to subtype C. Incorporating this historical sequence into phylogenetic models demonstrated that divergence time estimates derived from post-1978 genomes are not systematically biased. Instead, variations in divergence times reflect natural phylogenetic stochasticity across HIV-1 subsets. Evolutionary analyses incorporating the specimen date the origin of the pandemic HIV-1 lineage to between 1881 and 1918. This archival genome acts as an ancient genetic calibrator that directly validates current models of HIV-1 evolutionary history.
Direct biological records of HIV-1 prior to the 1980s are exceedingly rare, leaving evolutionary and epidemiological models dependent on extrapolations from modern genomes. By providing physical genetic evidence from 1966, this work confirms the reliability of molecular clock models and establishes that the pandemic virus began spreading in humans around the turn of the twentieth century.
The abstract does not indicate a commercial application pathway, as the work represents early-stage basic research focused on evolutionary genomics and historical phylogenetic calibration.
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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.
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DOI: 10.1073/pnas.1913682117
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