Evidence map›Paper›PMID 33316731›Full record

ArticleVirology2021

Vulnerable targets in HIV-1 Pol for attenuation-based vaccine design.

Doty B A Ojwach, Paradise Madlala, Michelle Gordon, Thumbi Ndung'u, Jaclyn K Mann

Open access · greenAbstract read

In one paragraph

Article in Virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

0.1field-weighted citation impact, top 50% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

First report of computational protein-ligand docking to evaluate susceptibility to HIV integrase inhibitors in HIV-infected Iranian patients.Biochemistry and biophysics reports · 2022
Article

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

5 authors at 2 institutions in 2 countries.

Doty B A OjwachHIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.

Paradise MadlalaHIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.

Michelle GordonKwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Department of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

Thumbi Ndung'uHIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Africa Health Research Institute, Durban, South Africa; Max Planck Institute for Infection Biology, Berlin, Germany; Division of Infection and Immunity, University College London, London, UK.

Jaclyn K MannHIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa. Electronic address: mannj@ukzn.ac.za.

University of KwaZulu-Natal · ZAAfrica Health Research Institute · ZA

Funding

Pathogenesis of Clade C HIV InfectionR37AI067073 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI WALKER, BRUCE D · 2011 to 2020

$6.6M

NIAID NIH HHS R37 AI067073

6 · The paper itself

Abstract

Identification of viral immune escape mutations that compromise HIV's ability to replicate may aid rational attenuation-based vaccine design. Previously we reported amino acids associated with altered viral replication capacity (RC) from a sequence-function analysis of 487 patient-derived RT-integrase sequences. In this study, site-directed mutagenesis experiments were performed to validate the effect of these mutations on RC. Viral reverse transcripts were measured by quantitative PCR and structural modelling was performed to gain further insight into the effect of reverse transcriptase (RT) mutations on reverse transcription. RT-integrase variants in or flanking cytotoxic T cell epitopes in the RT palm (158S), RT thumb (241I and 257V) and integrase catalytic core domain (124N) were confirmed to significantly reduce RC. RT mutants showed a delayed initiation of viral DNA synthesis. Structural models provide insight into how these attenuating RT mutations may affect amino acid interactions in the helix clamp, primer grip and catalytic site regions.

Indexed as

AIDS VaccinesCatalytic DomainCell LineEpitopes, T-LymphocyteGenes, polHIV-1HIV IntegraseHIV Reverse TranscriptaseHumansModels, MolecularMutagenesis, Site-DirectedMutationProtein ConformationReal-Time Polymerase Chain ReactionReverse TranscriptionT-Lymphocytes, CytotoxicAIDS VaccinesEpitopes, T-LymphocyteHIV IntegraseHIV Reverse TranscriptaseVaccines, AttenuatedHIV-1 RT-IntegraseReplication capacitySequence modellingSite-directed mutagenesis

Identifiers

PMID33316731

DOI10.1016/j.virol.2020.12.003

PMCPMC7931244

OpenAlexW3113003200

What OpenQuestion holds

Textmetadata

LicenceTDM

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.