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Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors

Overview of attention for article published in Virology Journal, November 2017
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Title
Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors
Published in
Virology Journal, November 2017
DOI 10.1186/s12985-017-0887-1
Pubmed ID
Authors

Karolin Meixenberger, Kaveh Pouran Yousef, Maureen Rebecca Smith, Sybille Somogyi, Stefan Fiedler, Barbara Bartmeyer, Osamah Hamouda, Norbert Bannert, Max von Kleist, Claudia Kücherer

Abstract

Detailed knowledge of the evolutionary potential of polymorphic sites in a viral protein is important for understanding the development of drug resistance in the presence of an inhibitor. We therefore set out to analyse the molecular evolution of the HIV-1 subtype B integrase at the inter-patient level in Germany during a 20-year period prior to the first introduction of integrase strand inhibitors (INSTIs). We determined 337 HIV-1 integrase subtype B sequences (amino acids 1-278) from stored plasma samples of antiretroviral treatment-naïve individuals newly diagnosed with HIV-1 between 1986 and 2006. Shannon entropy was calculated to determine the variability at each amino acid position. Time trends in the frequency of amino acid variants were identified by linear regression. Direct coupling analysis was applied to detect covarying sites. Twenty-two time trends in the frequency of amino acid variants demonstrated either single amino acid exchanges or variation in the degree of polymorphy. Covariation was observed for 17 amino acid variants with a temporal trend. Some minor INSTI resistance mutations (T124A, V151I, K156 N, T206S, S230 N) and some INSTI-selected mutations (M50I, L101I, T122I, T124 N, T125A, M154I, G193E, V201I) were identified at overall frequencies >5%. Among these, the frequencies of L101I, T122I, and V201I increased over time, whereas the frequency of M154I decreased. Moreover, L101I, T122I, T124A, T125A, M154I, and V201I covaried with non-resistance-associated variants. Time-trending, covarying polymorphisms indicate that long-term evolutionary changes of the HIV-1 integrase involve defined clusters of possibly structurally or functionally associated sites independent of selective pressure through INSTIs at the inter-patient level. Linkage between polymorphic resistance- and non-resistance-associated sites can impact the selection of INSTI resistance mutations in complex ways. Identification of these sites can help in improving genotypic resistance assays, resistance prediction algorithms, and the development of new integrase inhibitors.

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Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 28%
Student > Master 7 24%
Other 2 7%
Researcher 2 7%
Professor 1 3%
Other 2 7%
Unknown 7 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 24%
Agricultural and Biological Sciences 4 14%
Medicine and Dentistry 3 10%
Immunology and Microbiology 3 10%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Other 3 10%
Unknown 8 28%

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 08 September 2018.
All research outputs
#11,954,650
of 13,483,547 outputs
Outputs from Virology Journal
#2,019
of 2,193 outputs
Outputs of similar age
#228,523
of 265,101 outputs
Outputs of similar age from Virology Journal
#1
of 1 outputs
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