Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 22, Pages 12222-12229Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1913682117
Keywords
HIV-1; evolution; virus; phylogeny
Categories
Funding
- NIH/National Institute of Allergy and Infectious Diseases (NIAID) [R01AI084691]
- David and Lucile Packard Foundation
- European Molecular Biology Organization (EMBO) long-term postdoctoral fellowship [ALTF-328]
- OUTGOING [Pegasus]2 Marie Sklodowska-Curie Fellowship of the Research Foundation-Flanders [12T1117N]
- European Research Council under the European Union's Horizon 2020 research and innovation programme [725422-ReservoirDOCS]
- Research Foundation-Flanders [G066215N, G0D5117N, G0B9317N]
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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), from1966 (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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