The unusual transmission genetics of RNA viruses pose unique opportunities for the design of anti-viral compounds. High polymerase error rates lead to high variability in the population of RNA genomes. However, the polyploid nature of viral infections leads to variations in selection pressure on different regions of RNA genomes, the consequences of which are unexplored. I hypothesize that differences in selection pressures will lead to differences in the observed rates of reversions of lethal mutations depending on the genetic behavior of the encoded viral product. Using poliovirus as a model system, a method to map reversion rates across the viral genome will be developed. The goal of this work is to produce a general method to map reversion rates for any positive-strand RNA virus, to identify regions of the genome likely to encode cis-acting RNAs and proteins, trans-acting monomers, or trans-acting oligomeric proteins, and to locate genetically stable elements of the viral genome for targeting by anti-viral compounds. If the predicted differences in reversion rates are found, the same method will be applied to bovine viral diarrhea virus (BVDV), a homolog of hepatitis C virus (HCV). Finally, the effects of anti-viral compounds on the evolution and replication of these viruses will be tested.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI050296-01
Application #
6405323
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Johnson, Leslye D
Project Start
2001-08-01
Project End
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
Stanford University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305