Abstract

The application will examine the mechanism of strand transfer carried out by HIV-1. Specific experiments include examination of the role of RNAse H of the viral RT in the process of transfer. Additionally, the roles of RT in promoting a transfer reaction and the influence of experimental conditions and viral nucleocapsid protein on the reaction will be determined. The investigator will determine the frequency of mutations accompanying homologous versus nonhomologous recombination. Mutations associated with the transfer reaction will be correlated to specific sequence features on the donor template. Examination of strand transfer efficiency and mutagenesis in the presence of Nevirapine will determine whether that drug alters the efficiency of strand transfer in mutagenesis. Drug resistant mutant RT will be used for analysis of strand transfer parameters and mutagenesis. These results will indicate whether drug treatment or drug induced RT mutations can promote or suppress viral recombination.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM049573-10
Application #
2883014
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1992-12-01
Project End
2000-03-31
Budget Start
1999-03-01
Budget End
2000-03-31
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Piekna-Przybylska, Dorota; Sullivan, Mark A; Sharma, Gaurav et al. (2014) U3 region in the HIV-1 genome adopts a G-quadruplex structure in its RNA and DNA sequence. Biochemistry 53:2581-93
Muchiri, John M; Li, Dongge; Dykes, Carrie et al. (2013) Efavirenz stimulates HIV-1 reverse transcriptase RNase H activity by a mechanism involving increased substrate binding and secondary cleavage activity. Biochemistry 52:4981-90
Piekna-Przybylska, Dorota; Sharma, Gaurav; Bambara, Robert A (2013) Mechanism of HIV-1 RNA dimerization in the central region of the genome and significance for viral evolution. J Biol Chem 288:24140-50
Amie, Sarah M; Daly, Michele B; Noble, Erin et al. (2013) Anti-HIV host factor SAMHD1 regulates viral sensitivity to nucleoside reverse transcriptase inhibitors via modulation of cellular deoxyribonucleoside triphosphate (dNTP) levels. J Biol Chem 288:20683-91
Nguyen, Laura A; Daddacha, Waaqo; Rigby, Sean et al. (2012) Altered strand transfer activity of a multiple-drug-resistant human immunodeficiency virus type 1 reverse transcriptase mutant with a dipeptide fingers domain insertion. J Mol Biol 415:248-62
Piekna-Przybylska, Dorota; Dykes, Carrie; Demeter, Lisa M et al. (2011) Sequences in the U3 region of human immunodeficiency virus 1 improve efficiency of minus strand transfer in infected cells. Virology 410:368-74
Shen, Wen; Gorelick, Robert J; Bambara, Robert A (2011) HIV-1 nucleocapsid protein increases strand transfer recombination by promoting dimeric G-quartet formation. J Biol Chem 286:29838-47
Piekna-Przybylska, Dorota; Bambara, Robert A (2011) Requirements for efficient minus strand strong-stop DNA transfer in human immunodeficiency virus 1. RNA Biol 8:230-6
Muchiri, John M; Rigby, Sean T; Nguyen, Laura A et al. (2011) HIV-1 reverse transcriptase dissociates during strand transfer. J Mol Biol 412:354-64
Piekna-Przybylska, Dorota; DiChiacchio, Laura; Mathews, David H et al. (2010) A sequence similar to tRNA 3 Lys gene is embedded in HIV-1 U3-R and promotes minus-strand transfer. Nat Struct Mol Biol 17:83-9

Showing the most recent 10 out of 58 publications