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Enhancer dependence of polyomavirus persistence in mouse kidneys
R Rochford1, J P Moreno, M L Peake
1Department of Molecular Biology and Biochemistry, University of California, Irvine.
Journal of Virology
|June 1, 1992
Summary
Polyomavirus enhancer sequences influence viral DNA replication during acute and persistent infections. Enhancer variants can differentially affect infection levels and organ tropism, impacting disease outcomes.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Polyomavirus enhancer sequences are known to modulate viral DNA replication levels and organ specificity during acute infections.
- Previous research demonstrated the impact of enhancer sequence alterations on acute polyomavirus infection in newborn mice.
Purpose of the Study:
- To investigate whether polyomavirus enhancer sequence alterations affect viral DNA replication during the persistent phase of infection in vivo.
- To determine if enhancer-mediated effects on acute infection correlate with persistent infection outcomes.
- To explore the relationship between enhancer variants, persistent infection states, and associated pathology.
Main Methods:
- Infection of newborn mice with a mixture of three distinct polyomavirus enhancer variants.
- Analysis of viral DNA replication levels and organ specificity during both acute and persistent phases.
- Histopathological examination of infected organs to assess disease severity and long-term effects.
Main Results:
- Organs demonstrated selection for enhancer-specific viral DNA replication during both acute and persistent infection phases.
- High-level acute infection in certain organs (e.g., pancreas) did not guarantee a persistent infection in those same organs.
- Some enhancer variants established high-level persistent kidney infections, invariably associated with significant histopathology and stunted growth (runting) in the mice.
- Persistent kidney infections appear to exist in distinct pathological (high-level) and non-pathological (low-level) states, influenced by the viral enhancer sequence.
Conclusions:
- Polyomavirus enhancers differentially impact acute and persistent infection dynamics.
- The viral enhancer sequence plays a critical role in determining the state of persistent infection, particularly in the kidneys, distinguishing between pathological and non-pathological outcomes.
- Enhancer-driven alterations in viral replication can lead to distinct pathological consequences during long-term infection.