Journal article
Macrophage-tropic HIV-1 variants from brain demonstrate alterations in the way gp120 engages both CD4 and CCR5
H Salimi, M Roche, N Webb, LR Gray, K Chikere, J Sterjovski, A Ellett, SL Wesselingh, PA Ramsland, B Lee, MJ Churchill, PR Gorry
Journal of Leukocyte Biology | WILEY | Published : 2013
DOI: 10.1189/jlb.0612308
Abstract
BR-derived HIV-1 strains have an exceptional ability to enter macrophages via mechanisms involving their gp120 Env that remain incompletely understood. Here, we used cell-based affinity-profiling methods and mathematical modeling to generate quantitative VERSA metrics that simultaneously measure Env-CD4 and Env- CCR5 interactions. These metrics were analyzed to distinguish the phenotypes of M-tropic and non-M-tropic CCR5-using HIV-1 variants derived from autopsy BRs and LNs, respectively. We show that highly M-tropic Env variants derived from brain can be defined by two distinct and simultaneously occurring phenotypes. First, BR-derived Envs demonstrated an enhanced ability to interact with ..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This study was supported, in part, by grants from the NHMRC to P. R. G., M.J.C., and S. L. W. (#603708 and #1006534) and by a grant from U.S. National Institutes of Health/NIAID to B. L. (R21 AI092218). H. S. is supported by a postgraduate research scholarship from the Iranian Ministry of Health and Medical Education. P. A. R. is the Sir Zelman Cowen Senior Research Fellow (Sir Zelman Cowen Fellowship Fund, Burnet Institute). P. R. G. is the recipient of an Australian NHMRC Level 2 Biomedical Career Development Award. L. R. G. is the recipient of an Australian NHMRC Early Career Research Fellowship. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute. We thank J. Sodroski for providing JR-CSF, YU2, Delta KS Env, pCMV Delta P1 Delta envpA, and pHIV-1Luc plasmids. We thank D. Kabat for providing JC53 cells, H. Hoshino for permission to use NP2-CD4 cells, and D. Mosier and R. Nedellec for supplying the NP2-CD4 cells. We also thank J. Sodroski and R. Doms for providing CCR5 mutants, D. Gabuzda for providing primary HIV-1 isolates, and D. Burton for providing the b12 mAb. The following reagent was obtained through the U.S. National Institutes of Health AIDS Research and Reference Reagent Program, Division of AIDS, NIAID: HIV-1 gp120 mAb (17b) from Dr. James E. Robinson.