Engineering of Lactobacillus jensenii to secrete RANTES and a CCR5 antagonist analogue as live HIV-1 blockers.

Abstract

The development of effective microbicides for the prevention of HIV-1 sexual transmission represents a primary goal for the control of AIDS epidemics worldwide. A promising strategy is the use of bacteria belonging to the vaginal microbiota as live microbicides for the topical production of HIV-1 inhibitors. We have engineered a human vaginal isolate of Lactobacillus jensenii to secrete the anti-HIV-1 chemokine RANTES, as well as C1C5 RANTES, a mutated analogue that acts as a CCR5 antagonist and therefore is devoid of proinflammatory activity. Full-length wild-type RANTES and C1C5 RANTES secreted by L. jensenii were purified to homogeneity and shown to adopt a correctly folded conformation. Both RANTES variants were shown to inhibit HIV-1 infection in CD4(+) T cells and macrophages, displaying strong activity against HIV-1 isolates of different genetic subtypes. This work provides proof of principle for the use of L. jensenii-produced C1C5 RANTES to block HIV-1 infection of CD4(+) T cells and macrophages, setting the basis for the development of a live anti-HIV-1 microbicide targeting CCR5 in an antagonistic manner.

• Authors: Luca Vangelista, Massimiliano Secchi, Xiaowen Liu, Angela Bachi, Letong Jia, Qiang Xu, Paolo Lusso
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 54 Issue 7 Pg. 2994-3001 (Jul 2010) ISSN: 1098-6596 [Electronic] United States
• PMID: 20479208 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-HIV Agents
• CCR5 Receptor Antagonists
• Chemokine CCL5

Topics

• Anti-HIV Agents (metabolism, pharmacology, therapeutic use)
• Blotting, Western
• CCR5 Receptor Antagonists
• Cells, Cultured
• Chemokine CCL5 (genetics, metabolism, therapeutic use)
• Chromatography, Ion Exchange
• HIV Infections (prevention & control, virology)
• HIV-1 (drug effects)
• Humans
• Lactobacillus (genetics, metabolism)