Evidence map›Paper›PMID 24023819›Full record

ArticlePloS one2013

Nef-specific CD8+ T cell responses contribute to HIV-1 immune control.

Emily Adland, Jonathan M Carlson, Paolo Paioni, Henrik Kløverpris, Roger Shapiro, Anthony Ogwu, Lynn Riddell, Graz Luzzi, Fabian Chen, Thambiah Balachandran and 8 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

29 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  3. T-Follicular-Like CD8Frontiers in immunology · 2022
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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

18 authors at 12 institutions in 5 countries.

Emily AdlandDepartment of Paediatrics, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
Jonathan M Carlson
Paolo Paioni
Henrik Kløverpris
Roger Shapiro
Anthony Ogwu
Lynn Riddell
Graz Luzzi
Fabian Chen
Thambiah Balachandran
David Heckerman
Anette Stryhn
Anne Edwards
Thumbi Ndung'u
Bruce D Walker
Søren Buus
Philip Goulder
Philippa C Matthews
University of Oxford · GBUniversity of Copenhagen · DKMicrosoft (United States) · USBotswana Harvard AIDS Institute Partnership · BWChurchill Hospital · GBHarvard University · USHoward Hughes Medical Institute · USLuton and Dunstable Hospital · GBNorthampton General Hospital NHS Trust · GBRagon Institute of MGH, MIT and Harvard · USRoyal Berkshire Hospital · GBWycombe General Hospital · GB

Funding

Optimizing CD8+ T-cell responses against C clade HIV infection in subSaharan AfriR01AI046995 · NIAID · UNIVERSITY OF OXFORD · PI GOULDER, PHILIP J · 2000 to 2014
$6.8M
Medical Research Council G0501777NIAID NIH HHS R01 AI046995NIAID NIH HHS R01 AI46995Wellcome Trust
6 · The paper itself

Abstract

Recent studies in the SIV-macaque model of HIV infection suggest that Nef-specific CD8+ T-cell responses may mediate highly effective immune control of viraemia. In HIV infection Nef recognition dominates in acute infection, but in large cohort studies of chronically infected subjects, breadth of T cell responses to Nef has not been correlated with significant viraemic control. Improved disease outcomes have instead been associated with targeting Gag and, in some cases, Pol. However analyses of the breadth of Nef-specific T cell responses have been confounded by the extreme immunogenicity and multiple epitope overlap within the central regions of Nef, making discrimination of distinct responses impossible via IFN-gamma ELISPOT assays. Thus an alternative approach to assess Nef as an immune target is needed. Here, we show in a cohort of >700 individuals with chronic C-clade infection that >50% of HLA-B-selected polymorphisms within Nef are associated with a predicted fitness cost to the virus, and that HLA-B alleles that successfully drive selection within Nef are those linked with lower viral loads. Furthermore, the specific CD8+ T cell epitopes that are restricted by protective HLA Class I alleles correspond substantially to effective SIV-specific epitopes in Nef. Distinguishing such individual HIV-specific responses within Nef requires specific peptide-MHC I tetramers. Overall, these data suggest that CD8+ T cell targeting of certain specific Nef epitopes contributes to HIV suppression. These data suggest that a re-evaluation of the potential use of Nef in HIV T-cell vaccine candidates would be justified.

Indexed as

AdultAmino Acid SequenceCD8-Positive T-LymphocytesConserved SequenceEvolution, MolecularHIV-1HLA-B AntigensHumansImmunizationMolecular Sequence DataMutationnef Gene Products, Human Immunodeficiency VirusPolymorphism, GeneticSelection, GeneticViral LoadHLA-B Antigensnef Gene Products, Human Immunodeficiency Virusnef protein, Human immunodeficiency virus 1

Identifiers

PMID24023819
PMCPMC3759414
OpenAlexW2155999541

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.