As detection methods become more sophisticated, there is an increasing realization that viruses can reside within apparently normal hosts for extended periods. During such long-term infections, virus reactivation may occur spontaneously or after changes in the immunological status of the host. The onset of virus replication may initiate pathogenic events by provoking immune responses against the virus and virus infected cells and/or from virus disruption of cellular functions. The significance of long-term infections for human disease processes is only now becoming fully apparent and there have been several suggestions that viruses may be involved with chronic degenerative diseases. At present, there is only limited understanding of the molecular events associated with the establishment and maintenance of long-term virus infections both with respect to alterations in virus gene expression and virus-induced changes within the infected individual. I intend to study a well-characterized and reproducible model system, based on persistent infections of laboratory mice and tissue culture cells with lymphocytic choriomeningitis virus, to identify regulatory events that mediate the transition from acute to persistent infection and subsequent maintenance of the persistent infection. A detailed explanation for the molecular basis of virus persistence in one system will allow conceptual developments for the whole field of virus persistence and may suggest strategies for intervention and eventual clearance of a persistent infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025224-07
Application #
3138625
Study Section
Experimental Virology Study Section (EVR)
Project Start
1989-07-01
Project End
1995-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
7
Fiscal Year
1993
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
Meyer, B J; Southern, P J (1997) A novel type of defective viral genome suggests a unique strategy to establish and maintain persistent lymphocytic choriomeningitis virus infections. J Virol 71:6757-64
Zeller, J C; Nguyen, N; Southern, P J (1997) Differential immune recognition of LCMV nucleoprotein and glycoprotein in transgenic mice expressing LCMV cDNA genes. Virology 231:290-300
Butz, E A; Hostager, B S; Southern, P J (1994) Macrophages in mice acutely infected with lymphocytic choriomeningitis virus are primed for nitric oxide synthesis. Microb Pathog 16:283-95
Butz, E A; Southern, P J (1994) Lymphocytic choriomeningitis virus-induced immune dysfunction: induction of and recovery from T-cell anergy in acutely infected mice. J Virol 68:8477-80
Meyer, B J; Southern, P J (1994) Sequence heterogeneity in the termini of lymphocytic choriomeningitis virus genomic and antigenomic RNAs. J Virol 68:7659-64
Meyer, B J; Southern, P J (1993) Concurrent sequence analysis of 5' and 3' RNA termini by intramolecular circularization reveals 5' nontemplated bases and 3' terminal heterogeneity for lymphocytic choriomeningitis virus mRNAs. J Virol 67:2621-7
Southern, P J; Dyrberg, T; Schwimmbeck, P L et al. (1990) Persistent virus infection and development of virus-induced disease. J Autoimmun 3 Suppl 1:13-20
Fuller-Pace, F V; Southern, P J (1989) Detection of virus-specific RNA-dependent RNA polymerase activity in extracts from cells infected with lymphocytic choriomeningitis virus: in vitro synthesis of full-length viral RNA species. J Virol 63:1938-44
Francis, S J; Southern, P J (1988) Deleted viral RNAs and lymphocytic choriomeningitis virus persistence in vitro. J Gen Virol 69 ( Pt 8):1893-902