| Engineering of Lactobacillus jensenii to secrete RANTES and a CCR5 antagonist analogue as live HIV-1 blockers. | |
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MedLine Citation:
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PMID: 20479208 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Luca Vangelista; Massimiliano Secchi; Xiaowen Liu; Angela Bachi; Letong Jia; Qiang Xu; Paolo Lusso |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-05-17 |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 54 ISSN: 1098-6596 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-17 Completed Date: 2010-09-21 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: United States |
Other Details:
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Languages: eng Pagination: 2994-3001 Citation Subset: IM |
Affiliation:
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Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy. vangelista.luca@hsr.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anti-HIV Agents
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metabolism,
pharmacology,
therapeutic use* Blotting, Western Cells, Cultured Chemokine CCL5 / genetics, metabolism*, therapeutic use* Chromatography, Ion Exchange HIV Infections / prevention & control*, virology HIV-1 / drug effects* Humans Lactobacillus / genetics, metabolism* Receptors, CCR5 / antagonists & inhibitors* |
| Grant Support | |
ID/Acronym/Agency:
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1U19AI060615/AI/NIAID NIH HHS; 5R21AI079799/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Chemokine CCL5; 0/Receptors, CCR5 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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