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Polyomavirus replication in mice: influences of VP1 type and route of inoculation
T W Dubensky1, R Freund, C J Dawe
1Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Abstract:
Patterns of polyomavirus replication and spread have been studied following inoculation of virus into newborn mice. Levels of virus replication in different tissues were followed in situ by using whole mouse section blots and immunoperoxidase staining for the major capsid protein VP1, as well as by tissue extraction and direct quantitation of viral DNA and infectious virus. Patterns of replication and spread were compared between the "high tumor" strain (inducing a high incidence of tumors) PTA and and the "low tumor" strain (inducing a low incidence of tumors) RA, following different routes of inoculation. The ability to induce a high tumor profile correlated with the ability to establish disseminated productive infection, with the kidney as a major site of amplification. Furthermore, results with PTA-RA recombinant viruses and site-directed mutants showed that the VP1 specificity of PTA, demonstrated earlier to be a critical determinant for induction of a high tumor profile (R. Freund, A. Calderone, C. J. Dawe, and T. L. Benjamin, J. Virol. 65:335-341, 1991), is also critical for amplification in the kidney and for establishment of disseminated infections.
Insights
Polyomavirus strains differ in tumor development. High tumor-inducing polyomaviruses spread widely, with kidneys amplifying infection, a trait linked to the VP1 protein. This VP1 specificity is key for kidney amplification and widespread infection.
Area of Science:
- Virology
- Oncology
- Immunology
Background:
- Polyomaviruses are DNA tumor viruses with diverse pathogenic potentials.
- Understanding polyomavirus replication and spread is crucial for disease prevention and treatment.
Purpose of the Study:
- To investigate the replication and spread patterns of different polyomavirus strains in newborn mice.
- To determine the role of the major capsid protein VP1 in polyomavirus pathogenesis and tissue tropism.
Main Methods:
- In situ hybridization (whole mouse section blots) and immunoperoxidase staining for VP1.
- Tissue extraction and direct quantitation of viral DNA and infectious virus.
- Comparison of high tumor (PTA) and low tumor (RA) strains, including recombinant viruses and site-directed mutants.
Main Results:
- High tumor-inducing polyomavirus strains establish disseminated productive infections, with kidneys as a major amplification site.
- VP1 specificity of the PTA strain is critical for kidney amplification and disseminated infection.
- Kidney amplification and disseminated infection correlate with the ability to induce a high tumor profile.
Conclusions:
- VP1 specificity is a critical determinant for polyomavirus dissemination and amplification in the kidney.
- The ability to establish widespread productive infection, particularly in the kidney, is linked to high tumor incidence.
- These findings provide insights into polyomavirus oncogenesis and host-organ interactions.