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CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity



CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity



Antiviral Research 39(3): 175-187



The natural CC-chemokine RANTES(3-68), missing two NH2-terminal residues, has been isolated from leukocytes and tumor cells. The highly specific aminopeptidase dipeptidyl peptidase IV (DPP IV), also called CD26, was shown to be responsible for this NH2-terminal truncation of RANTES. 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. This 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 no anti-HIV-1 activity (IC50 > 130 nM), whereas RANTES(3 - 68) was a potent inhibitor of HIV-1 replication (IC50: 5.5 nM). The anti-HIV-1 activity of RANTES(1-68) in the different cell types correlated with the expression 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 important role of CD26-mediated processing of RANTES in inhibiting the replication of CCR5-binding HIV strains in HIV-infected persons and in preventing the development of AIDS.

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Accession: 010262810

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PMID: 9833958

DOI: 10.1016/s0166-3542(98)00039-4



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