Journal article
HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less-efficient mechanism of gp120-CCR5 engagement that attenuates macrophage tropism
M Roche, MR Jakobsen, J Sterjovski, A Ellett, F Posta, B Lee, B Jubb, M Westby, SR Lewin, PA Ramsland, MJ Churchill, PR Gorry
Journal of Virology | Published : 2011
DOI: 10.1128/JVI.00106-11
Abstract
Maraviroc (MVC) inhibits the entry of human immunodeficiency virus type 1 (HIV-1) by binding to and modifying the conformation of the CCR5 extracellular loops (ECLs). Resistance to MVC results from alterations in the HIV-1 gp120 envelope glycoproteins (Env) enabling recognition of the drug-bound conformation of CCR5. To better understand the mechanisms underlying MVC resistance, we characterized the virus-cell interactions of gp120 from in vitro-generated MVC-resistant HIV-1 (MVC-Res Env), comparing them with those of gp120 from the sensitive parental virus (MVC-Sens Env). In the absence of the drug, MVC-Res Env maintains a highly efficient interaction with CCR5, similar to that of MVC-Sens ..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This study was supported by a grant from the Australian Center for HIV and Hepatitis Virology Research (ACH2) to P. R. G. and M.J.C. and by a grant from NIH/NIAID to B. L. (R21 AI092218). M. R. is supported by a Monash University Postgraduate Research Scholarship. P. R. G. is the recipient of an Australian National Health and Medical Research Council (NHMRC) Level 2 Biomedical Career Development award. P. A. R. is the recipient of an NHMRC R. Douglas Wright Biomedical Career Development award. S. R. L. is the recipient of an NHMRC Practitioner Fellowship. We gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program, received by the Burnet Institute.