Multiple residues in the extracellular domains of CCR3 are critical for coreceptor activity.
Human immunodeficiency virus type 1 (HIV-1) binds to the human CD4 (hCD4) and a coreceptor to enter permissive human cells. The chemokine receptors, hCCR5 and hCXCR4, are the primary coreceptors used by HIV-1 isolates in vivo, however, hCCR3 has been implicated as a coreceptor for HIV infection of the central nervous system. To determine the domains and amino acids important in hCCR3 coreceptor activity, chimeras between the permissive hCCR3 and the non-permissive rhesus macaque CCR3 (RhCCR3) were constructed and assessed for coreceptor activity for two R5 strains of HIV-1 (YU-2 and ADA) and one R5X4 strain (89.6). Even though three extracellular domains of CCR3 participated in coreceptor activity for the two R5 isolates (ECD-1, ECD-3, and ECD-4), for the R5X4 isolate, ECD-4, and to a lesser extent ECD-3, were critical for coreceptor activity. In addition, residues 13 and 20 in ECD-1, residue 179 in ECD-3, and residue in 271 in ECD-4 of CCR3 were identified for HIV-1 envelope-mediated entry for R5 isolates. In contrast, all the residues on ECD-4 appeared necessary for coreceptor activity for HIV-1(89.6). Therefore, multiple residues on multiple extracellular domains of hCCR3 are important for coreceptor activity for HIV-1.
Department of Biology, School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA. phong.ho@duke.edu
Phong T
PT
Ho
Benjamin E
BE
Teal
Ted M
TM
Ross
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D017354:Point Mutation; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins
C515350:CCR3 protein, human; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins