Multiple extracellular elements of CCR5 and HIV-1 entry: dissociation from response to chemokines.
The human beta-chemokine receptor CCR5 is an important cofactor for entry of human immunodeficiency virus-type 1 (HIV-1). The murine form of CCR5, despite its 82 percent identity to the human form, was not functional as an HIV-1 coreceptor. HIV-1 entry function could be reconstituted by fusion of various individual elements derived from the extracellular region of human CCR5 onto murine CCR5. Analysis of chimeras containing elements from human CCR5 and human CCR2B suggested that a complex structure rather than single contact sites is responsible for facilitation of viral entry. Further, certain chimeras lacking the domains necessary to signal in response to their natural chemokine ligands retained vigorous HIV-1 coreceptor activity.
Atchison
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Gladstone Institute of Virology and Immunology, School of Medicine, University of California, San Francisco, Post Office Box 419100, San Francisco, CA 94141-9100, USA. mark_goldsmith@quickmail.ucsf.edu
Gosling
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Monteclaro
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Franci
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Digilio
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Charo
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Goldsmith
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D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D019556:COS Cells; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008024:Ligands; D051379:Mice; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
C515334:CCR2 protein, human; D015704:CD4 Antigens; C515335:Ccr2 protein, mouse; D007295:Inositol Phosphates; D008024:Ligands; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins