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Journal of Virology, August 2000, p. 6893-6910, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Use of Inhibitors To Evaluate Coreceptor Usage by Simian and Simian/Human Immunodeficiency Viruses and Human Immunodeficiency Virus Type 2 in Primary Cells

Yi-jun Zhang,1 Bernard Lou,1 Renu B. Lal,2 Agegnehu Gettie,1 Preston A. Marx,1,3 and John P. Moore1,*

Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 100161; National Center for Infectious Diseases, DASTLR, Centers for Disease Control and Prevention, Atlanta, Georgia 303332; and Tulane University Medical Center, New Orleans, Louisiana 704333

Received 21 January 2000/Accepted 2 May 2000

We have used coreceptor-targeted inhibitors to investigate which coreceptors are used by human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency viruses (SIV), and human immunodeficiency virus type 2 (HIV-2) to enter peripheral blood mononuclear cells (PBMC). The inhibitors are TAK-779, which is specific for CCR5 and CCR2, aminooxypentane-RANTES, which blocks entry via CCR5 and CCR3, and AMD3100, which targets CXCR4. We found that for all the HIV-1 isolates and all but one of the HIV-2 isolates tested, the only relevant coreceptors were CCR5 and CXCR4. However, one HIV-2 isolate replicated in human PBMC even in the presence of TAK-779 and AMD3100, suggesting that it might use an undefined, alternative coreceptor that is expressed in the cells of some individuals. SIVmac239 and SIVmac251 (from macaques) were also able to use an alternative coreceptor to enter PBMC from some, but not all, human and macaque donors. The replication in human PBMC of SIVrcm (from a red-capped mangabey), a virus which uses CCR2 but not CCR5 for entry, was blocked by TAK-779, suggesting that CCR2 is indeed the paramount coreceptor for this virus in primary cells.

* Corresponding author. Present address: Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021. Phone: (212) 746-4462. Fax: (212) 746-8340. E-mail: jpm2003{at}med.cornell.edu.

Journal of Virology, August 2000, p. 6893-6910, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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