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

Overview of attention for article published in BMC Infectious Diseases, October 2015
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Title
Impact of naturally occurring amino acid variations on the detection of HIV-1 p24 in diagnostic antigen tests
Published in
BMC Infectious Diseases, October 2015
DOI 10.1186/s12879-015-1174-7
Pubmed ID
Authors

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

Abstract

The 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. Using 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. Changing 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.

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Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 33%
Student > Master 4 19%
Student > Bachelor 3 14%
Student > Ph. D. Student 2 10%
Professor 1 5%
Other 2 10%
Unknown 2 10%
Readers by discipline Count As %
Medicine and Dentistry 5 24%
Agricultural and Biological Sciences 4 19%
Immunology and Microbiology 3 14%
Biochemistry, Genetics and Molecular Biology 2 10%
Veterinary Science and Veterinary Medicine 1 5%
Other 3 14%
Unknown 3 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 October 2015.
All research outputs
#4,810,194
of 6,504,996 outputs
Outputs from BMC Infectious Diseases
#2,242
of 3,034 outputs
Outputs of similar age
#141,717
of 206,854 outputs
Outputs of similar age from BMC Infectious Diseases
#127
of 164 outputs
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