Coronaviruses are positive-strand RNA viruses that cause respiratory infections in humans and important gastrointestinal and neurologic disease in other animal species. Mouse hepatitis virus (MHV) is a model for studies of coronavirus replication and pathogenesis. The central goal of the proposed research is to define interactions of mouse hepatitis virus with host cells during formation and function of viral replication complexes. MHV directs viral RNA synthesis on membranous replication complexes that are distributed thoughout the cytoplasm. These complexes are distinct from sites ofvirion assembly in the intermediate compartment of the Golgi (ERGIC). Proteins processed from the replicase gene polyprotein localize with the nucleocapsid (N) protein at sites of viral RNA synthesis in two closely associated protein complexes, the p22/p65 complex and the hel/N complex. At late times of infection, the hel/N complexes separate from the p22/p65 complexes and translocate to sites of virion assembly in the ERGIC. However, the precise composition of replication complexes is not known, and the mechanism of hel/N complex translocation has not been determined. This proposal describes an integrated research program to define the organization and translocation of MHV replication complexes.
In Specific Aim 1, the protein and membrane composition of MHV replication complexes will be determined. In Speeific Aim 2, the mechanism of hel/N complex translocation to the ERGIC will be defined.
In Specific Aim 3, the functions of viral proteins in replication complex translocation will be determined. These studies will identify fundamental mechanisms by which MHV directs replication complex formation and function and will define virus-cell interactions that are essential for successful virus replication.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050083-05
Application #
7152568
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Park, Eun-Chung
Project Start
2002-12-15
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2008-11-30
Support Year
5
Fiscal Year
2007
Total Cost
$286,350
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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