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 en try of human immunodeficiency virus-type 1 (HIV-1), The murine form of CCR5, despite its 82 percent identity to the human form, was not func tional as an HIV-1 coreceptor. HIV-1 entry function could be reconstit uted by fusion of various individual elements derived from the extrace llular region of human CCR5 onto murine CCR5. Analysis of chimeras con taining elements from human CCR5 and human CCR2B suggested that a comp lex structure rather than single contact sites is responsible for faci litation of viral entry, Further, certain chimeras lacking the domains necessary to signal in response to their natural chemokine ligands re tained vigorous HIV-1 coreceptor activity.