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. 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 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. 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.
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. 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 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. 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.
Authors: A Trkola; T J Ketas; K A Nagashima; L Zhao; T Cilliers; L Morris; J P Moore; P J Maddon; W C Olson Journal: J Virol Date: 2001-01 Impact factor: 5.103
Authors: W C Olson; G E Rabut; K A Nagashima; D N Tran; D J Anselma; S P Monard; J P Segal; D A Thompson; F Kajumo; Y Guo; J P Moore; P J Maddon; T Dragic Journal: J Virol Date: 1999-05 Impact factor: 5.103
Authors: A Trkola; C Gordon; J Matthews; E Maxwell; T Ketas; L Czaplewski; A E Proudfoot; J P Moore Journal: J Virol Date: 1999-08 Impact factor: 5.103
Authors: Fotini Tsamis; Svetlana Gavrilov; Francis Kajumo; Christoph Seibert; Shawn Kuhmann; Tom Ketas; Alexandra Trkola; Anadan Palani; John W Clader; Jayaram R Tagat; Stuart McCombie; Bahige Baroudy; John P Moore; Thomas P Sakmar; Tatjana Dragic Journal: J Virol Date: 2003-05 Impact factor: 5.103