Metraipolis › archive › dc_f1ef334cd86d

A de novo approach to inferring within-host fitness effects during untreated HIV-1 infection — Europe PMC PMID:32492061

Source: Europe PMC (en)
Original: https://europepmc.org/article/MED/32492061
DOI: 10.1371/journal.ppat.1008171
License (as archived): CC0-1.0
Archived: 2026-11-08T13:42:33.822Z
SHA-256 of the archived text: 3ea55e80b670e7733d2e282ca777fc3ad8e5deb48defe79e05576b447bdeb4b3
Stable URL of this page: https://metraipolis.com/documento/dc_f1ef334cd86d

How to cite

A de novo approach to inferring within-host fitness effects during untreated HIV-1 infection — Europe PMC PMID:32492061 — Europe PMC (en), https://europepmc.org/article/MED/32492061 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_f1ef334cd86d (Metraipolis archive dc_f1ef334cd86d, sha256 3ea55e80b670e7733d2e282ca777fc3ad8e5deb48defe79e05576b447bdeb4b3)

BibTeX

@misc{dcf1ef334cd86d,
  title = {A de novo approach to inferring within-host fitness effects during untreated HIV-1 infection — Europe PMC PMID:32492061},
  howpublished = {Europe PMC (en)},
  url = {https://europepmc.org/article/MED/32492061},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_f1ef334cd86d; sha256 3ea55e80b670e7733d2e282ca777fc3ad8e5deb48defe79e05576b447bdeb4b3},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC (en), https://europepmc.org/article/MED/32492061. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

In the absence of effective antiviral therapy, HIV-1 evolves in response to the within-host environment, of which the immune system is an important aspect. During the earliest stages of infection, this process of evolution is very rapid, driven by a small number of CTL escape mutations. As the infection progresses, immune escape variants evolve under reduced magnitudes of selection, while competition between an increasing number of polymorphic alleles (i.e., clonal interference) makes it difficult to quantify the magnitude of selection acting upon specific variant alleles. To tackle this complex problem, we developed a novel multi-locus inference method to evaluate the role of selection during the chronic stage of within-host infection. We applied this method to targeted sequence data from the p24 and gp41 regions of HIV-1 collected from 34 patients with long-term untreated HIV-1 infection. We identify a broad distribution of beneficial fitness effects during infection, with a small number of variants evolving under strong selection and very many variants evolving under weaker selection. The uniquely large number of infections analysed granted a previously unparalleled statistical power to identify loci at which selection could be inferred to act with statistical confidence. Our model makes no prior assumptions about the nature of alleles under selection, such that any synonymous or non-synonymous variant may be inferred to evolve under selection. However, the majority of variants inferred with confidence to be under selection were non-synonymous in nature, and in most cases were have previously been associated with either CTL escape in p24 or neutralising antibody escape in gp41. We also identified a putative new CTL escape site (residue 286 in gag), and a region of gp41 (including residues 644, 648, 655 in env) likely to be associated with immune escape. Sites inferred to be under selection in multiple hosts have high within-host and between-host diversity although not all sites with high between-host diversity were inferred to be under selection at the within-host level. Our identification of selection at sites associated with resistance to broadly neutralising antibodies (bNAbs) highlights the need to fully understand the role of selection in untreated individuals when designing bNAb based therapies.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: PLoS pathogens, 2020 (prima pubblicazione 2020-06-03).
Identificativi: PMID 32492061 · PMCID PMC7295245 · DOI 10.1371/journal.ppat.1008171.
Descrittori MeSH principali: Models, Genetic; Selection, Genetic.
Pagina: https://europepmc.org/article/MED/32492061 — https://doi.org/10.1371/journal.ppat.1008171. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
Letto il 2026-11-08T13:38:21.521Z tramite l'API REST ufficiale di Europe PMC (EMBL-EBI), nel rispetto del robots.txt e del crawl-delay.