Document Detail


Engineering of Lactobacillus jensenii to secrete RANTES and a CCR5 antagonist analogue as live HIV-1 blockers.
MedLine Citation:
PMID:  20479208     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-05-17
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  54     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-17     Completed Date:  2010-09-21     Revised Date:  2011-07-19    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2994-3001     Citation Subset:  IM    
Affiliation:
Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy. vangelista.luca@hsr.it
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / 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:
1U19AI060615/AI/NIAID NIH HHS; 5R21AI079799/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Chemokine CCL5; 0/Receptors, CCR5
Comments/Corrections

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