Identification of compounds that modulate HIV-1 vpr protein acti

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

435 5, 530350, 530300, G01N 3353, C12Q 170, C07K 100, C07K 1400

Patent

active

058742255

ABSTRACT:
The present invention is directed toward methods of identifying compounds which inhibit the human immunodeficiency virus (HIV) viral protein R (Vpr) from stimulating the differentiation of undifferentiated cells. This invention takes advantage of the observation that cell lines from rhabdomyosarcomas, which are tumors of muscle origin, have been used as models of CD4-independent HIV infection. These cell lines can be induced to differentiate in vitro. The vpr gene of HIV-1 is sufficient for the differentiation of the human rhabdomyosarcoma cell line TE671. Differentiated cells are characterized by great enlargement, altered morphology, lack of replication, and high level expression of the muscle-specific protein myosin. Morphological differentiation and inhibition of proliferation of other transformed cell lines following vpr expression was also observed. This invention also relates toward methods of identifying compounds which inhibit HIV Vpr binding to Gag. These screening methods should facilitate the identification and development of antiviral agents.

REFERENCES:
Mitsuya et al., 1991, Faseb J. 5:2369-2381.
Bybee et al., 1991, Blood Rev. 5:177-192.
Scott et al., 1993, Int. J. Dev. Biol. 37:67-74.
Wiederman et al., 1993, J. Ped. Endocrin. 6:85-91.
Murphy et al., 1993, Molec. Neurobiol. 7:111-135.
Johnson, T., 1994, Pharmac. Ther. 62:247-265.
Bernardez-Clark et al., 1991, Protein Refolding, ACS, USA pp. 1-20.
Parker, C., 1990, Meth. Enzymol. 182:700-718.
Adachi, A., et al., Production of Acquired Immunodeficiency Syndrome-Associated Retrovirus in Human and Nonhuman Cells Transfected with an Infectious Molecular Clone (1986) J. Virol. 59:284-291.
Aguanno, S., et al., 12-0-Tetradecanoylphorbol-13-Acetate-induced Differentiation of a Human Rhabdomyosarcoma Cell Line (1990) Cancer Res. 50:3377-3382.
Arya, S.K., et al., Trans-Activator Gene of Human T-Lymphotropic Virus Type III (HTLV-III) (1985) Science 229:69-73.
Cohen, E.A., et al., Identification of HIV-1 vpr Product and Function (1990) J. Acquir. Immune Defic. Syndr. 3:11-18.
Cohen, E.A., et al., Human Immunodeficiency Virus vpr Product Is a Virion-Associated Regulatory Protein (1990) J. Virol. 64:3097-3099.
Fisher, A., A molecular clone of HTLV-III with biological activity 1985 Nature 316:262.
Harada, S., et al., Tumor Promoter, TPA, Enhances Replication of HTLV-III/LAV (1986) Virology 154:249-258.
Hattori, N., et al., The human immunodeficiency virus type 2 vpr gene is essential for productive infection of human macrophages (1990) Proc. Natl. Acad. Sci. USA 87:8080-8084.
Hiti, A.L., et al., Expression of the MyoDl Muscle Determination Gene Defines Differentiation Capability but Not tumorigenicity of Human Rhabdomyosarcomas (1989) Mol. Cell. Biol. 9:4722-4730.
Immonoassays for the 80's, A. Voller et al., Eds., University Park, 1981.
Kozak, M. Point Mutations Define a Sequence Flanking the AUG Initiator Codon That Modulates Translation by Eukaryotic Ribosomes (1986) Cell 44:283-292.
Ling, L.L., et al., Optimization of the Polymerase Chain Reaction with Regard to Fidelity: Modified T7, Taq, and Vent DNA Polymerases, (1991) PCR Meth. Appl. 1:63-69.
Morgenstern and Land, Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line, 1990 Nucl. Acids Res. 18(12):3587-3596.
Ogawa, K., et al., Mutational Analysis of the Human Immunodeficiency Virus vpr Open Reading Frame, (1989) J. Virol. 63:4110-4114.
Osol, A., Remington's Pharmaceutical Sciences.
Ratner, L. et al., Complete nucleotide sequence of the AIDS virus, HTLV-III, (1985) Science 313:277-284.
Ratner, L. et al., Complete Nucleotide Sequences of Functional Clones of the AIDS virus, (1987) AIDS Res. Hum. Retroviruses 3:57-69.
Sambrook et al., Molecular Cloning a Laboratory Manual, Second Ed. Cold Spring Harbor Press (1989).
Shibata, R., et al. Mutational Analysis of Simian Immunodeficiency Virus From African Green Monkeys and Human Immunodeficiency Virus Type 2, (1990a). J. Med. Primatol. 19:217-225.
Shibata, R., et al. Mutational Analysis of the Human Immunodeficiency Virus Type 2 (HIV-2) Genome in Relation to HIV-1 and Simian Immunodeficiency Virus SIV, (1990b) J. Virol. 64:742-747.
Siegel and Lukas, Morphological and biochemical differentiation of the human medulloblastoma cell line TE6781, (1988) Dev. Brain Res. 44:269-280.
Stacich, B. et al., Characterization of Long Terminal Repeat Sequences of HTLV-III, (1985) Science 227:538-540.
Stratton, M.R., et al., Characterization of the human cell line TE671, (1989) Carcinogenesis 10:899-905.
Work, T.S., et al., Laboratory Techniques and Biochemistry in Molecular Biology, North Holland Publishing Company, N.Y., 1978.
Wide, Radioimmune Assay Method, Kirkham, Ed., E. & S. Livingstone, Edinburgh, 1970, pp. 199-206.
Weiner, D.B., et al., Human Genes Other than CD4 Facilitate HIV-1 Infection of Murine Cells, (1991) Pathobiology 59:361-371.
Weiner, D.B., et al., Linkage of tyrosine kinase activity with transforming ability of the p185neu oncoprotein, (1989) Oncogene 4:1175-1183.
Wong-Staal, F., et al., Human Immunodeficiency Virus: The Eighth Gene, (1987) AIDS Res. Hum. Retroviruses 3:33-39.
Yu, X.F., et al. Open Reading Frame vpr of Simian Immunodeficiency Virus Encodes a Virion-Associated Protein, (1990) J. Virol. 64:5688-5693.
Yuan, X., et al., Human Immunodeficiency Virus vpr Gene Encodes a Virion-Associated Protein, (1990) AIDS Res. Hum. Retroviruses 6:1265-1271.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Identification of compounds that modulate HIV-1 vpr protein acti does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Identification of compounds that modulate HIV-1 vpr protein acti, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Identification of compounds that modulate HIV-1 vpr protein acti will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-305486

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.