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Journal of Virology, April 2003, p. 4449-4456, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4449-4456.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The CCR5 and CXCR4 Coreceptors Are Both Used by Human Immunodeficiency Virus Type 1 Primary Isolates from Subtype C

Tonie Cilliers,1 Jabulani Nhlapo,1 Mia Coetzer,1 Dragana Orlovic,2 Thomas Ketas,3 William C. Olson,3 John P. Moore,4 Alexandra Trkola,5 and Lynn Morris1*

AIDS Virus Research Unit, National Institute for Communicable Diseases,1 Sizwe Infectious Diseases Hospital, Johannesburg, South Africa,2 Progenics Pharmaceuticals Inc., Tarrytown,3 Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York,4 Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich, Switzerland5

Received 3 September 2002/ Accepted 23 December 2002

Human immunodeficiency virus type 1 (HIV-1) subtype C viruses with different coreceptor usage profiles were isolated from 29 South African patients with advanced AIDS. All 24 R5 isolates were inhibited by the CCR5-specific agents, PRO 140 and RANTES, while the two X4 viruses and the three R5X4 viruses were sensitive to the CXCR4-specific inhibitor, AMD3100. The five X4 or R5X4 viruses were all able to replicate in peripheral blood mononuclear cells that did not express CCR5. When tested using coreceptor-transfected cell lines, one R5 virus was also able to use CXCR6, and another R5X4 virus could use CCR3, BOB/GPR15, and CXCR6. The R5X4 and X4 viruses contained more-diverse V3 loop sequences, with a higher overall positive charge, than the R5 viruses. Hence, some HIV-1 subtype C viruses are able to use CCR5, CXCR4, or both CXCR4 and CCR5 for entry, and they are sensitive to specific inhibitors of entry via these coreceptors. These observations are relevant to understanding the rapid spread of HIV-1 subtype C in the developing world and to the design of intervention and treatment strategies.

* Corresponding author. Mailing address: AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa. Phone: 2711 321-4232. Fax: 2711 321-4234. E-mail: lynnm{at}niv.ac.za.

Journal of Virology, April 2003, p. 4449-4456, Vol. 77, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.7.4449-4456.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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