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Phenotypic co-receptor tropism and Maraviroc sensitivity in HIV-1 subtype C from East Africa
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 2363Article in journal (Refereed) Published
Abstract [en]

Genotypic tropism testing (GTT) for co-receptor usage is a recommended tool for clinical practice before administration of the CCR5-antagonist maraviroc. For some isolates, phenotypic tropism testing (PTT) revealed discordant results with GTT. In this study, we performed a comparative study between GTT and PTT in HIV-1C from East Africa (HIV-1C(EA)) and compared the data with HIV-1B and 01_AE and described the maraviroc susceptibility in the CCR5-tropic strains. Patient-derived HIV-1 envgp120 region was cloned into a modified pNL4-3 plasmid expressing the luciferase gene. rPhenotyping dissected single clones from 31 HIV-1C(EA) infected patients and four strains with known phenotype. Additionally, 68 clones from 18 patients (HIV-1B: 5, 01_AE: 7, HIV-1C(EA): 6) were used to determine the PTT in GHOST cell line. The respective V3-sequences were used for GTT. R5-tropic strains from HIV-1C(EA) (n = 20) and non-C (n = 12) were tested for maraviroc sensitivity in TZMbl cell line. The GTT falsely called a higher proportion of X4-tropic strains in HIV-1C(ET) compared to PTT by both rPhenotyping and the GHOST-cell assay. When multiple clones were tested in a subset of patients' samples, both dual-tropic and R5-tropic strains were identified for HIV-1C. Relatively higher EC50 values were observed in HIV-1C strains than the non-C strains (p = 0.002).

Place, publisher, year, edition, pages
Nature Publishing Group, 2018. Vol. 8, no 1, article id 2363
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:kth:diva-223512DOI: 10.1038/s41598-018-20814-2ISI: 000424087700035PubMedID: 29403064Scopus ID: 2-s2.0-85041657682OAI: oai:DiVA.org:kth-223512DiVA, id: diva2:1184793
Funder
Swedish Research Council, 2016-01675; 2017-01330Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180222

Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-02-22Bibliographically approved

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