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

• Published in: AIDS (London) Vol. 12; no. 9; pp. 977 - 984
• Main Authors: YLISASTIGUI, L, VIZZAVONA, J, DRAKOPOULOU, E, PAINDAVOINE, P, CALVO, C.-F, PARMENTIER, M, GLUCKMAN, J. C, VITA, C, BENJOUAD, A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 18.06.1998
• Subjects: AIDS/HIV; Animals; Anti-HIV Agents - metabolism; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Cells, Cultured; Chemokine CCL5 - chemical synthesis; Chemokine CCL5 - metabolism; Chemokine CCL5 - pharmacology; Chemotaxis; CHO Cells; Cricetinae; HIV-1 - physiology; Humans; Leukocytes, Mononuclear - physiology; Leukocytes, Mononuclear - virology; Macrophages - drug effects; Macrophages - physiology; Macrophages - virology; Medical sciences; Pharmacology. Drug treatments; Receptors, CCR5 - genetics; Receptors, CCR5 - metabolism; Immunopathology; HIV-1 virus; RANTES; Retroviridae; AIDS; Synthetic inhibitor; Immune deficiency; Lentivirus; In vitro; Biological activity; Infection; Virus; Chemokine; Viral disease; Antiviral; Human immunodeficiency virus; Antagonist; Infected cell; Macrophage
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-199809000-00004

To determine the effect of beta-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. Use of chemically synthesized molecules devoid of biological contaminants and monocyte-derived macrophages from healthy donors. 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. Whereas full-length and truncated RANTES derivatives bound to beta-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. 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.