The overall goal of this proposal is elucidation of key driving forces for evolution and mutagenesis of retroviruses. The hypothesis which is set forth is as follows: the dNTP substrate binding affinity of retroviral DNA polymerases, reverse transcriptases (RT), is a key determinant for 1) evolution rate and 2) cell type specificity of retroviruses. The fidelity ifference between RTs of two major groups of retroviruses, lentiviruses and onco-retroviruses is responsible for their mutatgenesis and evolution rate differences: In addition, onco-retroviruses exclusively infect dividing cells containing high cellular dNTP concentration, whereas lentiviruses uniquely infect non-dividing cells containing low dNTP concentrations as well as dividing cells. Therefore, the hypothesis is that dNTP binding affinity of RT is a determinant of cell type specificity of these two groups of retroviruses. This hypothesis will be tested using RTs from two retroviruses feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV), which are isolated from a single host species.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI056668-02
Application #
6795460
Study Section
Special Emphasis Panel (ZRG1-MBC-1 (29))
Program Officer
Hernandez, Milton J
Project Start
2003-12-01
Project End
2007-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
2
Fiscal Year
2005
Total Cost
$39,986
Indirect Cost
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Operario, Darwin J; Balakrishnan, Mini; Bambara, Robert A et al. (2006) Reduced dNTP interaction of human immunodeficiency virus type 1 reverse transcriptase promotes strand transfer. J Biol Chem 281:32113-21
Operario, Darwin J; Reynolds, Holly M; Kim, Baek (2005) Comparison of DNA polymerase activities between recombinant feline immunodeficiency and leukemia virus reverse transcriptases. Virology 335:106-21