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Journal of Virology, August 2000, p. 6946-6952, Vol. 74, No. 15
0022-538X/00/$04.00+0

CCR8 on Human Thymocytes Functions as a Human Immunodeficiency Virus Type 1 Coreceptor

Shirley Lee,1,dagger H. Lee Tiffany,2 Lisa King,1 Philip M. Murphy,2 Hana Golding,1 and Marina B. Zaitseva1,*

Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration,1 and Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health,2 Bethesda, Maryland 20892

Received 7 February 2000/Accepted 4 May 2000

To determine whether human immunodeficiency virus type 1 (HIV-1) coreceptors besides CXCR4 and CCR5 are involved in HIV-1 infection of the thymus, we focused on CCR8, a receptor for the chemokine I-309, because of its high expression in the thymus. Similar levels of CCR8 mRNA were detected in immature and mature primary human thymocytes. Consistent with this, [125I]I-309 was shown to bind specifically and with similar affinity to the surface of immature and mature human thymocytes. Fusion of human thymocytes with cells expressing HIV-1 X4 or X4R5 envelope glycoprotein was inhibited by I-309 in a dose-dependent manner. In addition, I-309 partially inhibited productive infection of human thymocytes by X4, R5, and X4R5 HIV-1 strains. Our data provide the first evidence that CCR8 functions as an HIV-1 coreceptor on primary human cells and suggest that CCR8 may contribute to HIV-1-induced thymic pathogenesis.

* Corresponding author. Mailing address: Division of Viral Products, FDA, CBER, Bldg. 29B, 8800 Rockville Pike, Bethesda, MD 20892. Phone: (301) 827-0736. Fax: (301) 496-1810. E-mail: zaitseva{at}cber.fda.gov.

dagger Present address: Department of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD 20850.

Journal of Virology, August 2000, p. 6946-6952, Vol. 74, No. 15
0022-538X/00/$04.00+0


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