We plan to study in detail a series of """"""""white pock"""""""" host range mutants of rabbit poxvirus (RPmu mutants) which in nonpermissive cells are blocked at many stages of viral development. As a major effort, we plan to continue our mapping studies on these mutants, which we have shown to be the result of deletions, by the use of restriction enzyme analysis. Our studies on the five mutants that we have examined have already implicated 17% of the viral genome in the host range phenonema. Our data show that these five mutants result in three different phenotypes in nonpermissive cells, offering the possiblity of correlating defined regions of the genome to a specific function. As a step in this direction, we plan to map the remaining 15 host range RPmu mutants in our collection and characterize them as to what steps in the synthesis and processing of macromolecules are blocked in the nonpermissive host and why. We also plan to extend our genetic mapping studies to include a series of """"""""white pock"""""""" nonhost range mutants, also probably deletions, which because they readily recombine with the host range mutants, should lie elsewhere on the genome. We have already biochemically characterized two mutants which appear to be blocked at the level of translation. We propose to study the mechanism of this translation block in detail. Three additional mutants are blocked at the level of morphogenesis, and synthesized aberrant virus-like particles different from one another. We plan to characterize the aberrant particles by biophysical and electron microsopic means, as well as by assay of virion-associated enzymatic activities. Since the existence of host range mutants reflects biochemical differances between cells, we hope to use our information to begin to explore these differences which allow the selective invasion of target organs and tissues in vivo and lead to the disease state asociated with a given viral infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015722-06
Application #
3126382
Study Section
Experimental Virology Study Section (EVR)
Project Start
1980-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
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Turner, Peter C; Moyer, Richard W (2006) The cowpox virus fusion regulator proteins SPI-3 and hemagglutinin interact in infected and uninfected cells. Virology 347:88-99
Nathaniel, Rajkumar; MacNeill, Amy L; Wang, Yun-Xiang et al. (2004) Cowpox virus CrmA, Myxoma virus SERP2 and baculovirus P35 are not functionally interchangeable caspase inhibitors in poxvirus infections. J Gen Virol 85:1267-78
Brum, Lauren M; Lopez, M Cecilia; Varela, Juan Carlos et al. (2003) Microarray analysis of A549 cells infected with rabbitpox virus (RPV): a comparison of wild-type RPV and RPV deleted for the host range gene, SPI-1. Virology 315:322-34

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