Polyomavirus Replicates in Differentiating but Not in Proliferating Tubules of Adult Mouse Polycystic Kidneys

Abstract

Previous observations led us to propose that ongoing cellular differentiation, rather then proliferation, may be needed for high-level polyomavirus (Py) replication in permissive organs in vivo. We further tested this proposal by using the C57BL/6J-cpk/cpk mouse model for the autosomal recessive form of polycystic kidney disease (PKD) because both cellular proliferation and differentiation continue into the adult kidney in separate and distinct regions of the kidneys, whereas normal adult kidneys are quiescent and nonpermissive to Py. Adult PKD mice inoculated with Py were assayed for Py DNA replication by in situ hybridization and Southern analysis and for viral gene expression by immunofluorescence 5 days postinfection. The proliferation of collecting duct tubules of PKD kidneys was confirmed by in situ autoradiography for tritiated thymidine incorporation but were observed to be nonpermissive for Py gene expression or replication. Normal differentiated collecting ducts, however, are capable of supporting Py replication in non-PKD runted mice (Rochford et al., 1992). Py DNA, large T-Ag, and VP1, however, were detected in the nonproliferating distal and proximal tubules of the PKD parenchyma. The parenchymal tissues appear to be differentiating in a compensatory response to cyst growth. These results further support the view that in vivo Py replication may require ongoing cellular differentiation rather then mitosis.