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J Virol, July 1998, p. 5425-5432, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Genetically Divergent Strains of Human Immunodeficiency Virus Type 2 Use Multiple Coreceptors for Viral Entry

Sherry M. Owen,1 Dennis Ellenberger,1 Mark Rayfield,1 Stefan Wiktor,2 Philippe Michel,3 Michael H. Grieco,4 Feng Gao,5 Beatrice H. Hahn,5 and Renu B. Lal1,*

Retrovirus Diseases Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 303331; Projet Retro-CI, Abidjan, Ivory Coast2; Centre de Recherches du Service de Sante des Armees, La Tronche Cedex, France3; St. Luke's-Roosevelt Hospital Center, New York, New York 100194; and Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 352945

Received 11 November 1997/Accepted 24 March 1998

Several members of the seven-transmembrane chemokine receptor family have been shown to serve, with CD4, as coreceptors for entry by human immunodeficiency virus type 1 (HIV-1). While coreceptor usage by HIV-1 primary isolates has been studied by several groups, there is only limited information available concerning coreceptor usage by primary HIV-2 isolates. In this study, we have analyzed coreceptor usage of 15 primary HIV-2 isolates, using lymphocytes from a donor with nonfunctional CCR5 (CCR5 -/-; homozygous 32-bp deletion). Based on the infections of PBMCs, seven of these primary isolates had an absolute requirement for CCR5 expression, whereas the remaining eight exhibited a broader coreceptor usage. All CCR5-requiring isolates were non-syncytium inducing, whereas isolates utilizing multiple coreceptors were syncytium inducing. Blocking experiments using known ligands for chemokine receptors provided indirect evidence for additional coreceptor utilization by primary HIV-2 isolates. Analysis of GHOST4 cell lines expressing various chemokine receptors (CCR1, CCR2b, CCR3, CCR4, CCR5, CXCR4, BONZO, and BOB) further defined specific coreceptor usage of primary HIV-2 isolates. The receptors used included CXCR4, CCR1-5, and the recently described receptors BONZO and BOB. However, the efficiency at which the coreceptors were utilized varied greatly among the various isolates. Analysis of V3 envelope sequences revealed no specific motif that correlated with coreceptor usage. Our data demonstrate that primary HIV-2 isolates are capable of using a broad range of coreceptors for productive infection in vitro. Additionally, our data suggest that expanded coreceptor usage by HIV-2 may correlate with disease progression.

* Corresponding author. Mailing address: MS G-19, Retrovirus Diseases Branch, CDC, 1600 Clifton Rd., Atlanta, GA 30333. Phone: (404) 639-1036. Fax: (404) 639-1174. E-mail: RBL3{at}CDC.GOV.

J Virol, July 1998, p. 5425-5432, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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