The magnitude of HIV-1 resistance to the CCR5 antagonist maraviroc may impart a differential alteration in HIV-1 tropism for macrophages and T-cell subsets

Flynn, J, Paukovics, G, Moore, M, Ellett, A, Gray, L, Duncan, R, Salimi, H, Jubb, B, Westby, M, Purcell, D, Lewin, S, Lee, B, Churchill, M, Gorry, P and Roche, M 2013, 'The magnitude of HIV-1 resistance to the CCR5 antagonist maraviroc may impart a differential alteration in HIV-1 tropism for macrophages and T-cell subsets', Virology, vol. 442, pp. 51-58.


Document type: Journal Article
Collection: Journal Articles

Title The magnitude of HIV-1 resistance to the CCR5 antagonist maraviroc may impart a differential alteration in HIV-1 tropism for macrophages and T-cell subsets
Author(s) Flynn, J
Paukovics, G
Moore, M
Ellett, A
Gray, L
Duncan, R
Salimi, H
Jubb, B
Westby, M
Purcell, D
Lewin, S
Lee, B
Churchill, M
Gorry, P
Roche, M
Year 2013
Journal name Virology
Volume number 442
Start page 51
End page 58
Total pages 8
Publisher Academic Press
Abstract Human immunodeficiency virus type 1 (HIV-1) resistance to CCR5 antagonists, including maraviroc (MVC), results from alterations in the HIV-1 envelope glycoproteins (Env) enabling recognition of antagonist-bound CCR5. Here, we characterized tropism alterations for CD4+ T-cell subsets and macrophages by Envs from two subjects who developed MVC resistance in vivo, which displayed either relatively efficient or inefficient recognition of MVC-bound CCR5. We show that MVC-resistant Env with efficient recognition of drug-bound CCR5 displays a tropism shift for CD4+ T-cell subsets associated with increased infection of central memory T-cells and reduced infection of effector memory and transitional memory T-cells, and no change in macrophage infectivity. In contrast, MVC-resistant Env with inefficient recognition of drug-bound CCR5 displays no change in tropism for CD4+ T-cell subsets, but exhibits a significant reduction in macrophage infectivity. The pattern of HIV-1 tropism alterations for susceptible cells may therefore be variable in subjects with MVC resistance.
Subject Virology
Medical Virology
Infectious Diseases
Cellular Immunology
Keyword(s) HIV-1
Maraviroc
Resistance
T-cell
Macrophage
Tropism
Env
gp120
DOI - identifier 10.1016/j.virol.2013.03.026
Copyright notice © 2013 Elsevier Inc. All rights reserved.
ISSN 0042-6822
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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