CUTTING EDGE - ENHANCED ANTI-HIV-1 ACTIVITY AND ALTERED CHEMOTACTIC POTENCY OF NH2-TERMINALLY PROCESSED MACROPHAGE-DERIVED CHEMOKINE (MDC) IMPLY AN ADDITIONAL MDC RECEPTOR

Posttranslational processing of chemokines increases (IL-8) or decreas es (monocyte chemotactic protein-1) their chemotactic potency. Macroph age-derived chemokine (MDC) attracts monocytes, dendritic cells, activ ated lymphocytes, and NK cells and has reportedly anti-HIV-1 activity. Here we report that truncation of MDC by deletion of two NH2-terminal residues resulted in impaired binding to CC chemokine receptor (CCR)4 the only identified MDC receptor sofar. Truncated MDC(3-69) failed to desensitize calcium mobilization by MDC(1-69) or thymus- and activati on-regulated chemokine (TARC), another CCR4 ligand. MDC(3-69) lacked H UT-78 T cell chemotactic activity but retained its capacity to attract monocytes and to desensitize chemotaxis, Compared with MDC(1-69), MDC (3-69) had weak but enhanced antiviral activity against M- and T-tropi c HIV-1 strains. Furthermore, both MDC forms failed to signal through the orphan receptors Bonzo/STRL33 and BOB/GPR15 and to desensitize RAN TES and stromal cell-derived factor (SDF)-1 responses In CCR5-transfec ted and CXC chemokine receptor (CXCR)4-transfected cells, respectively . These findings suggest that MDC recognizes another, yet unidentified , receptor. We conclude that minimal NH2-terminal truncation of MDC di fferentially affects its various immunologic functions.