Evidence map›Paper›PMID 26511217›Full record

ArticleBMC infectious diseases2015

Impact of naturally occurring amino acid variations on the detection of HIV-1 p24 in diagnostic antigen tests.

Beatrice N Vetter, Vanessa Orlowski, Christoph Niederhauser, Louise Walter, Jörg Schüpbach

Open access · goldAbstract read
In one paragraph

Article in BMC infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 36% 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

7 citing papers in PubMed, 16 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

5 authors at 3 institutions in 1 country.

Beatrice N VetterSwiss National Center for Retroviruses (SNCR), Institute of Medical Virology, University of Zürich, Zürich, Switzerland. vetter.beatrice@virology.uzh.ch.
Vanessa OrlowskiInstitute of Molecular Life Science, University of Zürich, Zürich, Switzerland. orlowski.vanessa@uzh.ch.
Christoph NiederhauserBlood Transfusion Service, Swiss Red Cross Berne (BSDSRK), Berne, Switzerland. christoph.niederhauser@bsd-be.ch.
Louise WalterOfficial Medicines Control Laboratory, Biologika, Swissmedic, Berne, Switzerland. louise.walter@swissmedic.ch.
Jörg SchüpbachSwiss National Center for Retroviruses (SNCR), Institute of Medical Virology, University of Zürich, Zürich, Switzerland. schupbach.jorg@virology.uzh.ch.
University of Zurich · CHSwissmedic · CHSwiss Red Cross · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe detection of HIV-1 p24 antigen in diagnostic tests relies on antibodies binding to conserved areas of the protein to cover the full range of HIV-1 subtypes. Using a panel of 43 different virus-like particles (VLPs) expressing Gag from clinical HIV-1 isolates, we previously found that some highly sensitive tests completely failed to detect p24 of certain VLPs, seemingly unrelated to their subtype. Here we aimed to investigate the reason for this failure, hypothesising that it might be due to single amino acid variations in conserved epitopes.

methodsUsing amino acid alignment, we identified single amino acid variations at position 16 or 170 of p24, unique to those VLPs that failed to be detected in certain diagnostic tests. Through DNA-mutagenesis, these amino acids were changed to ones more commonly found at these positions. The impact of these changes on p24 detection was tested in commercial diagnostic tests as well as by Western Blot and ELISA, using epitope-specific antibodies. RESULTS AND

conclusionsChanging positions 16 or 170 to consensus amino acids restored the detection of p24 by the investigated diagnostic tests as well as by epitope-specific antibodies in Western Blot and ELISA. Hence, single amino acid changes in conserved epitopes can lead to the failure of p24 detection and thus to false-negative results. To optimise HIV diagnostic tests, they should also be evaluated using isolates which harbour less-frequent epitope variants.

Indexed as

Amino AcidsReagent Kits, DiagnosticAIDS SerodiagnosisAntigens, ViralBlotting, WesternEnzyme-Linked Immunosorbent AssayEpitopesHIV-1HIV Core Protein p24HumansMutagenesis, Site-DirectedAmino AcidsAntigens, ViralEpitopesHIV Core Protein p24Reagent Kits, Diagnostic

Identifiers

PMID26511217
PMCPMC4625719
OpenAlexW1889879757

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Registered trials

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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.