CD26-PROCESSED RANTES(3-68), BUT NOT INTACT RANTES, HAS POTENT ANTI-HIV-1 ACTIVITY

The natural CC-chemokine RANTES(3-68), missing two NH2-terminal residu es, has been isolated from leukocytes and tumor cells, The highly spec ific aminopeptidase dipeptidyl peptidase IV (DPP IV), also called CD26 , was shown to be responsible for this NH2-terminal truncation of RANT ES. Here it is reported that CD26/DPP IV treatment of RANTES enhances its anti-HIV-1 activity. RANTES(3-68) inhibited infection of PBMC by M -tropic HIV-1 strains ten-fold more efficiently than intact RANTES, Th is difference in antiviral potency between intact and truncated RANTES was even more pronounced (at least 25-fold) in CCR5-transfected cell lines. In HOS.CD4.CCR5 transfected cells, RANTES(1-68) had virtually n o anti-HIV-1 activity (IC50 > 130 nM), whereas RANTES(3-68) was a pote nt inhibitor of HIV-1 replication (IC50: 5.5 nM). The anti-HIV-1 activ ity of RANTES(1-68) in the different cell types correlated with the ex pression of CD26, Moreover, the addition of soluble CD26 together with RANTES(1-68) significantly enhanced the antiviral activity of RANTES in HOS.CD4.CCR5 cells (IC50: 13 nM). These observations point to an im portant role of CD26-mediated processing of RANTES in inhibiting the r eplication of CCR5-binding HIV strains in HIV-infected persons and in preventing the development of AIDS. (C) 1998 Elsevier Science B.V. All rights reserved.