Synthetic full-length and truncated RANTES inhibit HIV-1 infection of primary macrophages


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Abstract

Objective:To determine the effect of β-chemokines on HIV-1 infection of primary macrophages, and to search for chemokine derivatives devoid of biological effects but efficient at protecting CD4+ T lymphocytes and macrophages against HIV-1.Design:Use of chemically synthesized molecules devoid of biological contaminants and monocyte-derived macrophages from healthy donors.Methods:Full-length RANTES was chemically synthesized together with three derivatives, truncated of seven, eight and nine amino acids at the amino-terminus ([8–68]RANTES, [9–68]RANTES and [10–68]RANTES), which were tested for their biological activity and antiviral effects.Results:Whereas full-length and truncated RANTES derivatives bound to β-chemokine receptor CCR-5 with the same affinity as recombinant RANTES, the truncated forms were not chemotactic and acted as CCR-5 antagonists in this respect, although a partial agonist effect was noted on cell metabolism. Full-length RANTES and [8–68]RANTES protected T lymphocytes and macrophages from infection by HIV-1, although 10-fold higher concentrations of the truncated analogues were necessary to achieve the same effect as full-length RANTES. With regard to the effect of RANTES on HIV-1 infection of primary macrophages, our results contrast with most previously reported data.Conclusion:These data indicate that through binding to CCR-5, truncated RANTES derivatives that are devoid of detectable biological effects may represent candidates as drugs to protect both lymphocytes and macrophages from HIV-1.

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