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

doi:10.1128/JVI.74.15.6893-6910.2000

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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 type1 (HIV-1), simian immunodeficiency viruses (SIV), and human immunodeficiencyvirus type 2 (HIV-2) to enter peripheral blood mononuclear cells(PBMC). The inhibitors are TAK-779, which is specific for CCR5and CCR2, aminooxypentane-RANTES, which blocks entry via CCR5and CCR3, and AMD3100, which targets CXCR4. We found that forall the HIV-1 isolates and all but one of the HIV-2 isolates tested,the only relevant coreceptors were CCR5 and CXCR4. However, oneHIV-2 isolate replicated in human PBMC even in the presence ofTAK-779 and AMD3100, suggesting that it might use an undefined,alternative coreceptor that is expressed in the cells of someindividuals. SIV_mac239 and SIV_mac251 (from macaques) were alsoable to use an alternative coreceptor to enter PBMC from some,but not all, human and macaque donors. The replication in humanPBMC of SIV_rcm (from a red-capped mangabey), a virus which usesCCR2 but not CCR5 for entry, was blocked by TAK-779, suggestingthat CCR2 is indeed the paramount coreceptor for this virus inprimarycells.

^* 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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