Evidence map›Paper›PMID 33952315›Full record

ArticleRetrovirology2021

Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa.

Omotayo Farinre, Kamini Gounder, Tarylee Reddy, Marcel Tongo, Jonathan Hare, Beth Chaplin, Jill Gilmour, Phyllis Kanki, Jaclyn K Mann, Thumbi Ndung'u

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 44% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 6 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 4 countries.

Omotayo FarinreHIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Kamini GounderHIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Tarylee ReddyBiostatistics Research Unit, South African Medical Research Council, Durban, South Africa.
Marcel TongoCentre of Research for Emerging and Re-Emerging Diseases (CREMER), Yaoundé, Cameroon.
Jonathan HareInternational AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory (HIL), Imperial College, London, UK.
Beth ChaplinDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jill GilmourInternational AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory (HIL), Imperial College, London, UK.
Phyllis KankiDepartment of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jaclyn K MannHIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Thumbi Ndung'uHIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa. thumbi.ndungu@ahri.org.ORCID 0000-0003-2962-3992
Harvard University · USInternational HIV/AIDS Alliance · GBUniversity of KwaZulu-Natal · ZAAfrica Health Research Institute · ZARagon Institute of MGH, MIT and Harvard · USSouth African Medical Research Council · ZA

Funding

Wellcome TrustWellcome Trust 107752/Z/15/Z
6 · The paper itself

Abstract

backgroundThe HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower.

resultsGag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02_AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa.

conclusionsAlthough prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02_AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02_AG and subtype A respectively, which may have relevance for vaccine strategies.

Indexed as

AdultAfrica, EasternAfrica, WesternCross-Sectional StudiesFemalegag Gene Products, Human Immunodeficiency VirusGenotypeHIV-1HIV InfectionsHIV ProteaseHumansMalePhylogenyRecombination, GeneticRetrospective StudiesVirus Replicationgag Gene Products, Human Immunodeficiency VirusHIV ProteaseHIV-1 recombinantsHIV-1 replication capacityHIV-1 subtypeHLA class I allelesSub-Saharan Africa

Identifiers

PMID33952315
PMCPMC8097975
OpenAlexW3159916013

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.