The primary goal of my dissertation research is to investigate mechanisms of reovirus cell entry and disassembly. Reoviruses are nonenveloped viruses that enter cells by receptor-mediated endocytosis. In the endocytic pathway, reovirus virions undergo acid-dependent proteolytic disassembly. The proposed experiments will allow an identification of viral genes that carry mutations responsible for growth in the presence of disassembly inhibitor ammonium chloride, elucidate the biological and structural alterations associated with ammonium-chloride resistance, and provide new insights into the molecular basis of acid-induced disassembly events required for reovirus entry into cells. The powerful reovirus genetics system, a rich panel of mutants, an existing knowledge of protein structure and function, and techniques available to advance this work offer assurance that these problems can be solved. This research will enhance an understanding of the role of endosomal acidification in reovirus cell entry and contribute new information about the physiology of the endocytic pathway.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI052492-03
Application #
6777530
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Hernandez, Milton J
Project Start
2002-08-01
Project End
2005-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
3
Fiscal Year
2004
Total Cost
$31,515
Indirect Cost
Name
Meharry Medical College
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
041438185
City
Nashville
State
TN
Country
United States
Zip Code
37208
Clark, Kimberly M; Wetzel, J Denise; Gu, Yingqi et al. (2006) Reovirus variants selected for resistance to ammonium chloride have mutations in viral outer-capsid protein sigma3. J Virol 80:671-81