HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry.

M Roche; MR Jakobsen; A Ellett; H Salimiseyedabad; B Jubb; M Westby; B Lee; SR Lewin; MJ Churchill; PR Gorry

Journal article

HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry.

M Roche, MR Jakobsen, A Ellett, H Salimiseyedabad, B Jubb, M Westby, B Lee, SR Lewin, MJ Churchill, PR Gorry

Retrovirology | BIOMED CENTRAL LTD | Published : 2011

DOI: 10.1186/1742-4690-8-89

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Abstract

Maraviroc (MVC) and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by the viral gp120 envelope (Env) glycoproteins. Resistance to CCR5 antagonists results from HIV-1 Env acquiring the ability to utilize the drug-bound conformation of CCR5. Selecting for HIV-1 resistance to CCR5-antagonists in vitro is relatively difficult. However, the CCR5-using CC1/85 strain appears to be uniquely predisposed to acquiring resistance to several CCR5 antagonists in vitro including MVC, vicriviroc and AD101. Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interacti..

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University of Melbourne Researchers

Michael Roche Author

Sharon Lewin Author

Paul Gorry Author

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Funding Acknowledgements

We thank J. Sodroski for providing pSVIII-YU2 Env plasmid and for providing pCMV Delta P1 Delta envpA and pHIV-1Luc plasmids. We also thank D. Kabat for providing JC53 cells, N. Shimizu and H. Hoshino for permission to use NP2-CD4/CCR5 cells, and D. Mosier and R. Nedellec for supplying the NP2-CD4/CCR5 cells. The following reagents were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: TZM-bl cells from Dr. John C. Kappes, Dr. Xiaoyun Wu and Tranzyme Inc.; U87-CD4/CCR5 cells from Dr. HongKui Deng and Dr. Dan R. Littman. This study was supported by a grant by the Australian Center for HIV and Hepatitis Virology Research (ACH2) to PRG and MJC, and by a grant from NIH/NIAID to BL (R21 AI092218). MR is supported by a Monash University Postgraduate Research Scholarship. PRG is the recipient of an Australian National Health and Medical Research Council (NHMRC) Level 2 Biomedical Career Development Award. SRL is the recipient of a NHMRC Practitioner Fellowship. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute.