Flowchart: Preparation: Ccr5
 


                 

Text Box: Praf2

Text Box: Mcp1


Text Box: Rante


       

Text Box: 7Nd


                                             

                                                

                                                                                     

Text Box: Mip1- alpha


Text Box: Ccr5Text Box: Ccr2West Nile virus

Hiv

Heart                                                   

Lupus

Aid

Sars

Text Box: EAMText Box: Pclb 

                  

2007/5/1-11

 

Antimicrob Agents Chemother. 2006 Apr;50(4):1497-509.

Links

Click here to read 
Preclinical Evaluation of Synthetic -2 RANTES as a Candidate Vaginal Microbicide To Target CCR5.

Kish-Catalone TM, Lu W, Gallo RC, Devico AL.

Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, S622, Baltimore, MD 21201. devico@umbi.umd.edu.

A potential strategy that can be used to combat the worldwide AIDS epidemic is the development of a vaginal microbicide that prevents the sexual transmission of human immunodeficiency virus type 1 (HIV-1). Certain CC chemokines, including RANTES, MIP-1alpha, and MIP-1beta, might facilitate the development of such microbicides since they potently suppress HIV-1 infection by binding to CCR5, the viral coreceptor used by most sexually transmitted strains of HIV-1 to enter host cells. In this study, we evaluated whether a CCR5-specific fragment of RANTES that lacks two N-terminal residues (-2 RANTES) and possesses especially potent HIV-1 suppressive activity has toxicity profiles conducive to the advancement of testing in candidate microbicide formulations. Analyses were carried out with a synthetic version of the chemokine, which was formulated with either Novasomes 7474, a nonphospholipid liposome, or methylcellulose gel. Dialysis studies demonstrated that the formulated -2 RANTES was released from both vehicles and retained anti-HIV-1 activity. Preclinical toxicity studies carried out with Swiss Webster mouse and New Zealand White rabbit vaginal irritation models demonstrated minimal inflammation and minimal adverse changes in cervicovaginal tissue integrity after short-term (10 min) and long-term (24 h) exposure to formulations containing up to 1 mg/ml of -2 RANTES. Similarly, no toxicity was observed with formulations of bioactive murine RANTES in the Swiss Webster mouse vaginal irritation model. Overall, these preclinical studies suggest that -2 RANTES is suitable for further testing as a candidate anti-HIV-1 microbicide

 

 


 

Gene. 2006 Apr 12;371(1):154-65. Epub 2006 Feb 14.

Related Articles, Links

Click here to read 
Genomic organization, expression profile, and characterization of the new protein PRA1 domain family, member 2 (PRAF2).

Fo CS, Coleman CS, Wallick CJ, Vine AL, Bachmann AS.

Cancer Research Center of Hawaii, University of Hawaii at Manoa, 1236 Lauhala Street, Honolulu, HI 96813, USA.

PRA1 domain family, member 2 (PRAF2) is a new 19 kDa protein with four putative transmembrane (TM) domains. PRAF2 (formerly designated JM4) belongs to a new protein family, which plays a role in the regulation of intracellular protein transport. Recently, PRAF2 was found to interact with the chemokine receptor CCR5 [Schweneker, M., Bachmann, A.S., Moelling, K., 2005. JM4 is a four-transmembrane protein binding to the CCR5 receptor. FEBS Lett. 579, 1751-1758]. In order to further study the function and regulation of PRAF2, we determined its genomic structure and its protein expression pattern in normal and cancerous human tissues. PRAF2 encodes a 178-residue protein, whose sequence is related to PRAF1 (PRA1/prenylin) and PRAF3 (JWA/GTRAP3-18). The human PRAF2 gene contains three exons separated by two introns and is located on human chromosome Xp11.23. The recombinant PRAF2 protein was readily expressed in Schneider 2 (S2) insect cells, and the native protein was detected in human tissues with strong expression in the brain, small intestine, lung, spleen, and pancreas. The protein was undetectable in tissue of the testes. Strong PRAF2 protein expression was also found in human tumor tissues of the breast, colon, lung, and ovary, with a weaker staining pattern in normal tissues of the same patient. Our studies show for the first time that the CCR5-interacting PRAF2 protein is expressed in several human tissues with a possible function in ER/Golgi transport and vesicular traffic.

PMID: 16481131 [PubMed - in process]

 

Antimicrob Agents Chemother. 2006 Apr;50(4):1497-509.

Links

Click here to read 
Preclinical Evaluation of Synthetic -2 RANTES as a Candidate Vaginal Microbicide To Target CCR5.

Kish-Catalone TM, Lu W, Gallo RC, Devico AL.

Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, S622, Baltimore, MD 21201. devico@umbi.umd.edu.

A potential strategy that can be used to combat the worldwide AIDS epidemic is the development of a vaginal microbicide that prevents the sexual transmission of human immunodeficiency virus type 1 (HIV-1). Certain CC chemokines, including RANTES, MIP-1alpha, and MIP-1beta, might facilitate the development of such microbicides since they potently suppress HIV-1 infection by binding to CCR5, the viral coreceptor used by most sexually transmitted strains of HIV-1 to enter host cells. In this study, we evaluated whether a CCR5-specific fragment of RANTES that lacks two N-terminal residues (-2 RANTES) and possesses especially potent HIV-1 suppressive activity has toxicity profiles conducive to the advancement of testing in candidate microbicide formulations. Analyses were carried out with a synthetic version of the chemokine, which was formulated with either Novasomes 7474, a nonphospholipid liposome, or methylcellulose gel. Dialysis studies demonstrated that the formulated -2 RANTES was released from both vehicles and retained anti-HIV-1 activity. Preclinical toxicity studies carried out with Swiss Webster mouse and New Zealand White rabbit vaginal irritation models demonstrated minimal inflammation and minimal adverse changes in cervicovaginal tissue integrity after short-term (10 min) and long-term (24 h) exposure to formulations containing up to 1 mg/ml of -2 RANTES. Similarly, no toxicity was observed with formulations of bioactive murine RANTES in the Swiss Webster mouse vaginal irritation model. Overall, these preclinical studies suggest that -2 RANTES is suitable for further testing as a candidate anti-HIV-1 microbicide.