CCR8 on human thymocytes functions as a human immunodeficiency virus type 1 coreceptor.
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, [(125)I]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.
Lee
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Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, National Institutes of Health, Bethesda, Maryland 20892, USA.
Tiffany
H L
HL
King
L
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Murphy
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PM
Golding
H
H
Zaitseva
M B
MB
D054402:Chemokine CCL1; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC / Q000378:metabolism / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002675:Child, Preschool; D015536:Down-Regulation; D015686:Gene Products, env / Q000378:metabolism; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D007223:Infant; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054401:Receptors, CCR8; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*
C065971:CCL1 protein, human; C103330:CCR8 protein, human; C515255:CXCL12 protein, human; D054402:Chemokine CCL1; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D015686:Gene Products, env; D012333:RNA, Messenger; D054401:Receptors, CCR8; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D015728:Receptors, HIV