The distribution and kinetics of polyomavirus in lungs of intranasally infected newborn mice

lThe primary cell types that sustain polyomavirus (Py) replication following intranasal infection as well as the nature of the host cellular response to Py were unknown. As this is an essential and specific site for virus entry, it seems likely that viral gene function must be adapted to these mucosal tissues. Using immunohistochemistry and in situ hybridization, we determined the cell types in the lung that support Py gene expression and replication following intranasal inoculation of newborn mice within 24 h of birth. Lungs were collected daily from days 1 to 10 postinfection for Py DNA and early T antigen analysis and for histological examination by H&E staining, using methods that preserve the delicate newborn lung architecture. Viral DNA was present in increasing quantities from 2 to 6 dpi in a subset of the Clara cells lining the inner lumen of the bronchi and bronchioles, while T antigen expression was present in a majority of the cells in the bronchi and bronchiole lumen. A distinct and transient pattern of hyperplasia was observed among the cells expressing T antigen and was present from 3 through 6 dpi. Py DNA-containing cells exfoliated into the bronchiole lumen and alveolar ducts, but Py T antigen was not detected in these cells. Py DNA was first detected at 2 dpi, increased through 6 dpi, and abruptly declined through 9 dpi at which time there was no sign of viral DNA in the lungs by in situ hybridization. An unusual infiltration of neutrophils began before the presence of exfoliated cells or Py replication and continued for 2-3 days and was followed by a lymphocytic infiltration at 8-10 dpi lasting 2-3 days. Neither the hyperplasia nor the neutrophil infiltration occurred following infection with the MOP1033 MT-AS or RB1 LT-Ag mutants of Py. In addition, both the neutrophil infiltration and the transient hyperplasia are in stark contrast to the heavy macrophage infiltration that follows infection of lungs with mouse adenovirus. Thus it appears that Py elicits a distinct host response pattern not seen with other DNA viral infections. (C) 2000 academic Press.