Elucidating the viral and host factors enabling the cross-species transmission of primate lentiviruses from simians to humans
Bibliographic record
Abstract
Abstract The HIV-1 epidemic originated from a cross-species transmission of a primate lentivirus from chimpanzees to humans near the turn of the 18 th century. Simian immunodeficiency viruses have been jumping between old world monkeys in West/Central Africa for thousands of years. So why did HIV-1 only emerge in the past century? This study examined the replicative fitness, transmission, restriction, and cytopathogenicity of 26 primate lentiviruses. Pairwise competitions of these primate lentiviruses revealed that SIVcpz had the highest replicative fitness in human or chimpanzee peripheral blood mononuclear cells, even higher fitness than HIV-1 group M strains responsible for 37 million infections worldwide. In contrast the “HIV-2 lineage” (SIVsmm, SIVmac, SIVagm, and HIV-2) had the lowest replicative fitness. SIVcpz strains were less inhibited by human restriction factors than the “HIV-2 lineage” strains, a restriction that was inversely correlated with replicative fitness. SIVcpz from the chimpanzee subspecies Pan troglodytes troglodytes ( Ptt ) was slightly more fit in human cells than the strains from Pt schweinfurthii ( Pts ). However, unlike all other primate lentiviruses (including the HIV-2 lineage), SIVcpz was nonpathogenic in human tonsillar tissue and did not deplete CD4+ T-cells, consistent with the slow or nonpathogenic disease observed in chimpanzees. Despite the close phylogenetic relationship between SIVcpz_Ptt and HIV-1, this epidemic was either caused by cross species transmission of a rare, undiscovered SIVcpz strain of higher virulence or higher virulence differentially evolved among HIV-1 subtypes during the human epidemic. Author summary Invasion of wild animal habitats by humans can have devastating consequences for the human population as evident by the HIV-1 and SARS-CoV-2 epidemics. With SARS-CoV-2, a recent zoonotic jump, likely from bats, will help to identify a coronavirus progenitor. In contrast, simian immunodeficiency virus (SIV) jumped into humans over 100 years ago from a possibly extinct sub-species of chimpanzees and/or extinct lineage of SIV. We examined replicative fitness and pathogenesis of 26 different primate lentiviruses in human and chimpanzee primary lymphoid cells from blood and within tonsils. SIV from a specific chimpanzee species and lowland gorillas were the most capable of infecting and replicating in human and chimp lymphoid cells but they did not result in the pathogenesis related to disease in humans. In contrast, SIV from other old world monkeys were pathogenic but could not replicate efficiently in human cells. We propose the main HIV-1 is derived from a distinct jump of a very rare SIV strain in chimps leading to AIDS pandemic.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".