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


METHODS
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 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.


CONCLUSIONS
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.
Ylisastigui
L
L
Université Paris VI, Centre National de la Recherche Scientifique, Faculté de Médecine Pitié-Salpêtrière, France.
Vizzavona
J
J
Drakopoulou
E
E
Paindavoine
P
P
Calvo
C F
CF
Parmentier
M
M
Gluckman
J C
JC
Vita
C
C
Benjouad
A
A
D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology; D016466:CHO Cells; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D002633:Chemotaxis; D006224:Cricetinae; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology / Q000821:virology*; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism
D019380:Anti-HIV Agents; D018946:Chemokine CCL5; C101594:RANTES (9-68); D019713:Receptors, CCR5