Abstract

The investigator proposes to characterize the HIV-1 Gag/y interaction in molecular detail in vitro, and to evaluate its role in the biology of HIV-1 infection. High-resolution footprinting and mutagenesis will be performed to map specific residues and structures in y required for binding of Gag, RNA dimerization, and other in vitro activities. RNA conformational changes induced by Gag binding will be investigated, and the investigator will determine how binding to individual sites promotes or regulates y functions. Mutant HIV-1 proviruses with defined defects in y will be created and tested for their effects on virus infectivity, RNA packaging fidelity, particle morphology, and the efficiency of reverse transcription. Finally, the investigator will test newly-identified heterologous RNA ligands that bind with greater affinity than y to HIV-1 Gag for their ability to replace the native y locus in HIV-1 RNA and to act as competitive trans-inhibitors of y function and virus replication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI040317-05
Application #
6169846
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Bridges, Sandra H
Project Start
1996-07-01
Project End
2001-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
5
Fiscal Year
2000
Total Cost
$283,374
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Bhosle, Sushma; Suppiah, Suganthi; Molinaro, Ross et al. (2010) Evaluation of cellular determinants required for in vitro xenotropic murine leukemia virus-related virus entry into human prostate cancer and noncancerous cells. J Virol 84:6288-96
Kumar, Naveen; Xin, Zhong-Tao; Liang, Yuhong et al. (2008) NF-kappaB signaling differentially regulates influenza virus RNA synthesis. J Virol 82:9880-9
Liang, Yuhong; Huang, Taoying; Ly, Hinh et al. (2008) Mutational analyses of packaging signals in influenza virus PA, PB1, and PB2 genomic RNA segments. J Virol 82:229-36
Gipson, Clay L; Xin, Zhong-Tao; Danzy, Shamika C et al. (2007) Functional characterization of yeast telomerase RNA dimerization. J Biol Chem 282:18857-63
Regan, John F; Liang, Yuying; Parslow, Tristram G (2006) Defective assembly of influenza A virus due to a mutation in the polymerase subunit PA. J Virol 80:252-61
Ly, Hinh; Schertzer, Mike; Jastaniah, Wasil et al. (2005) Identification and functional characterization of 2 variant alleles of the telomerase RNA template gene (TERC) in a patient with dyskeratosis congenita. Blood 106:1246-52
Liang, Yuying; Hong, Ying; Parslow, Tristram G (2005) cis-Acting packaging signals in the influenza virus PB1, PB2, and PA genomic RNA segments. J Virol 79:10348-55
Ly, Hinh; Calado, Rodrigo T; Allard, Paulette et al. (2005) Functional characterization of telomerase RNA variants found in patients with hematologic disorders. Blood 105:2332-9
Lin, Jue; Ly, Hinh; Hussain, Arif et al. (2004) A universal telomerase RNA core structure includes structured motifs required for binding the telomerase reverse transcriptase protein. Proc Natl Acad Sci U S A 101:14713-8
Ly, Hinh; Xu, Lifeng; Rivera, Melissa A et al. (2003) A role for a novel 'trans-pseudoknot' RNA-RNA interaction in the functional dimerization of human telomerase. Genes Dev 17:1078-83

Showing the most recent 10 out of 23 publications