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

Abstract

Although estimated to have emerged in humans in Central Africa in the early 1900s, HIV-1, the main causative agent of AIDS, was only discovered in 1983. 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 1,652 formalin-fixed paraffin-embedded tissue specimens collected for pathology diagnostics in Kinshasa, Democratic Republic of Congo (DRC), between 1959 and 1967. We report the near-complete genome of one positive from 1966 ("DRC66")-a non-recombinant 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 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 1978-2015, showing the inherent phylogenetic stochasticity across subsets of the real HIV-1 diversity. 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. SignificanceInferring the precise timing of the origin of the HIV/AIDS pandemic is of great importance because it offers insights into which factors did-or did not-facilitate the emergence of the causal virus. Previous estimates 2 have implicated rapid development during the early 20 th century in Central Africa, which wove onceisolated populations into a more continuous fabric. We recovered the first HIV-1 genome from the 1960s, and it provides direct evidence that HIV-1 molecular clock estimates spanning the last half-century are remarkably reliable. And, because this genome itself was sampled only about a half-century after the estimated origin of the pandemic, it empirically anchors this crucial inference with high confidence.

Divergence dating using mixed effects clock modelling: An application to HIV-1

“…1998) and 1960A (Worobey et al. 2008) and a newly obtained near complete genome from a DRC sample dating back to 1966 that clusters basal to subtype C (DRC66; Gryseels et al. 2019).…”

New Technological Developments in Identification and Monitoring of New and Emerging Infections

“…However, it was through the use of molecular clocks, calibrated with early blood samples from Central Africa, that it became clear that HIV likely first crossed the species barrier, and started to spread amongst humans, around the early part of the 20th century. This timing coincided with large colonial population disruptions, mining and urbanization in the then Belgian Congo ( Gryseels et al, 2020 ; Worobey et al, 2008 ). By studying the relatedness of simian immunodeficiency viruses from chimpanzee subspecies, Pan troglodytes troglodytes, it became apparent that they were the source of this cross-species transmission ( Gao et al, 1999 ).…”

“…This has been used to establish when particular infectious agents entered human populations. From such studies it emerged that HIV-1 has entered human populations likely before 1930 in central Africa ( Gryseels et al, 2020 ; Worobey et al, 2008 ) and that circulating human coronaviruses infections such OC-43 and NL-63 are likely the result of historic species jumps from bats ( Huynh et al, 2012 ; Vijgen et al, 2005 ).…”

The Usefulness of HIV-1p24 in Detecting the Presence of HIV Infection in Histopathology Tissue Specimens

“…The human immunodeficiency virus 1 (HIV-1), the main causative agent of acquired immune deficiency syndrome (AIDS), was discovered in 1983. 1 Since its discovery, it has become a global pandemic, having infected more than 70 million people and claiming more than 35 million lives. 2,3 HIV-1 is polymorphic in nature, with many genetically related variants, due to the complexity of its cDNA formation and its mutation-prone reverse transcriptase enzyme.…”