The induction of chronic polymyositis in mice by Coxsackievirus B1 (CVB1) provides a useful model of virus-induced autoimmunity and is highly relevant to human disease in that the clinical course and histopathology closely resemble human polymyositis. The model also encompasses many attributes associated with autoimmune diseases including tissue tropism, differences in susceptibility among inbred mouse strains, and obligate participation of T cells. Myopathic and nonmyopathic strains of CVB1 have been identified. Preliminary data indicate that CVB1 RNA persists in influenced muscle in the chronic stage of the disease when virus can no longer be recovered in culture. Detailed information on picornavirus genome organization coupled with the ability to clone infectious cDNA make this an ideal system to examine molecular mechanisms of pathogenesis. Initial studies will involve construction of cDNA clones and chimeras to examine in detail the persistence of CVB1 RNA in specific tissues using in situ hybridization and polymerase chain reaction techniques and determine the relationship between persistence and immunologic attack on skeletal muscle. The second set of experiments will explore what differences exist in the genomic RNA of myopathic and nonmyopathic CVB1 strains and which of these differences relate to the ability to cause chronic inflammation in muscle. The results of these experiments should provide important information that will enhance our understanding of the mechanism through which CVB1 induces an immunologically mediated myositis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI031101-01
Application #
3146115
Study Section
Virology Study Section (VR)
Project Start
1990-09-01
Project End
1993-07-31
Budget Start
1990-09-01
Budget End
1991-07-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455