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

Jacqueline Kaye Flynn, Geza Paukovics, Miranda S Moore, Anne Ellett, Lachlan Robert Gray, Renee Duncan, Hamid Salimi, Becky Jubb, Mike Westby, Damian F J Purcell, Sharon R Lewin, Benhur Lee, Melissa Churchill, Paul R Gorry, Michael John Roche

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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. ? 2013 Elsevier Inc.
Original languageEnglish
Pages (from-to)51 - 58
Number of pages8
JournalVirology
Volume422
Issue number1
DOIs
Publication statusPublished - 2013

Cite this

Flynn, Jacqueline Kaye ; Paukovics, Geza ; Moore, Miranda S ; Ellett, Anne ; Gray, Lachlan Robert ; Duncan, Renee ; Salimi, Hamid ; Jubb, Becky ; Westby, Mike ; Purcell, Damian F J ; Lewin, Sharon R ; Lee, Benhur ; Churchill, Melissa ; Gorry, Paul R ; Roche, Michael John. / 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. In: Virology. 2013 ; Vol. 422, No. 1. pp. 51 - 58.
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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",
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. ? 2013 Elsevier Inc.",
author = "Flynn, {Jacqueline Kaye} and Geza Paukovics and Moore, {Miranda S} and Anne Ellett and Gray, {Lachlan Robert} and Renee Duncan and Hamid Salimi and Becky Jubb and Mike Westby and Purcell, {Damian F J} and Lewin, {Sharon R} and Benhur Lee and Melissa Churchill and Gorry, {Paul R} and Roche, {Michael John}",
year = "2013",
doi = "10.1016/j.virol.2013.03.026",
language = "English",
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pages = "51 -- 58",
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Flynn, JK, Paukovics, G, Moore, MS, Ellett, A, Gray, LR, Duncan, R, Salimi, H, Jubb, B, Westby, M, Purcell, DFJ, Lewin, SR, Lee, B, Churchill, M, Gorry, PR & Roche, MJ 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. 422, no. 1, pp. 51 - 58. https://doi.org/10.1016/j.virol.2013.03.026

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, Jacqueline Kaye; Paukovics, Geza; Moore, Miranda S; Ellett, Anne; Gray, Lachlan Robert; Duncan, Renee; Salimi, Hamid; Jubb, Becky; Westby, Mike; Purcell, Damian F J; Lewin, Sharon R; Lee, Benhur; Churchill, Melissa; Gorry, Paul R; Roche, Michael John.

In: Virology, Vol. 422, No. 1, 2013, p. 51 - 58.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 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

AU - Flynn, Jacqueline Kaye

AU - Paukovics, Geza

AU - Moore, Miranda S

AU - Ellett, Anne

AU - Gray, Lachlan Robert

AU - Duncan, Renee

AU - Salimi, Hamid

AU - Jubb, Becky

AU - Westby, Mike

AU - Purcell, Damian F J

AU - Lewin, Sharon R

AU - Lee, Benhur

AU - Churchill, Melissa

AU - Gorry, Paul R

AU - Roche, Michael John

PY - 2013

Y1 - 2013

N2 - 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. ? 2013 Elsevier Inc.

AB - 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. ? 2013 Elsevier Inc.

UR - http://www.sciencedirect.com/science/article/pii/S0042682213001797

U2 - 10.1016/j.virol.2013.03.026

DO - 10.1016/j.virol.2013.03.026

M3 - Article

VL - 422

SP - 51

EP - 58

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -