Hiv
Aid
Sars
Gene.
2006 Apr 12;371(1):154-65. Epub
2006 Feb 14. Antimicrob Agents Chemother.
2006 Apr;50(4):1497-509. Antimicrob Agents Chemother.
2006 Apr;50(4):1497-509.
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]
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
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.