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Characterization of the cell type-specific determinant in the genome of minute virus of mice
J P Antonietti1, R Sahli, P Beard
1Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland.
Abstract:
Two strains of minute virus of mice (MVM) show different host cell specificities. The prototype strain MVM(p) grows in fibroblasts, whereas the immunosuppressive variant MVM(i) grows in T lymphocytes. In this study, we have mapped on the viral genome a cell type-specific determinant: it is located between 69 and 85 map units in a region coding for the viral capsid proteins. The DNA of MVM(p) does not replicate in lymphocytes. MVM(i) cannot help MVM(p) grow in lymphocytes; thus the determinant acts in a cis fashion. We did not detect viral mRNA during a restrictive infection of lymphocytes with MVM(p). However, when the same cells were transfected with cloned DNA, both MVM(p) and MVM(i) DNAs were transcribed with the same efficiency from both promoters and the RNA was processed normally. Therefore, the specificity determinant is not a cell type-specific enhancer.
Insights
Minute virus of mice (MVM) strains exhibit distinct cell specificities. A viral genome region encoding capsid proteins determines MVM(p) fibroblast tropism versus MVM(i) T lymphocyte tropism, acting in cis.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Minute virus of mice (MVM) exists in strains with differing host cell specificities.
- The prototype strain MVM(p) infects fibroblasts, while the immunosuppressive variant MVM(i) infects T lymphocytes.
Purpose of the Study:
- To map the viral genome determinant responsible for cell type-specific tropism in MVM.
- To elucidate the mechanism by which MVM achieves differential host cell recognition.
Main Methods:
- Genetic mapping of the MVM genome to identify the region controlling cell specificity.
- Replication assays in fibroblasts and T lymphocytes using MVM(p) and MVM(i).
- Analysis of viral mRNA transcription and RNA processing in transfected lymphocytes.
Main Results:
- A cell type-specific determinant was localized to map units 69-85 of the MVM genome, within the capsid protein-coding region.
- MVM(p) DNA failed to replicate in T lymphocytes, and MVM(i) could not rescue MVM(p) replication, indicating a cis-acting determinant.
- Viral mRNA was undetectable during restrictive MVM(p) infection of lymphocytes, but both MVM(p) and MVM(i) DNAs were efficiently transcribed in transfected cells.
Conclusions:
- The cell type-specific determinant for MVM tropism resides in the viral capsid protein-coding region and acts in cis.
- The determinant does not function as a cell type-specific enhancer, as transcription occurred normally upon DNA transfection.
- This finding provides insight into the molecular mechanisms underlying parvovirus host cell tropism and immune evasion.