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

lThe primary cell types that sustain polyomavirus (Py) replication followin g 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 ent ry, it seems likely that viral gene function must be adapted to these mucos al tissues. Using immunohistochemistry and in situ hybridization, we determ ined the cell types in the lung that support Py gene expression and replica tion 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 D NA 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 an d bronchiole lumen. A distinct and transient pattern of hyperplasia was obs erved among the cells expressing T antigen and was present from 3 through 6 dpi. Py DNA-containing cells exfoliated into the bronchiole lumen and alve olar ducts, but Py T antigen was not detected in these cells. Py DNA was fi rst detected at 2 dpi, increased through 6 dpi, and abruptly declined throu gh 9 dpi at which time there was no sign of viral DNA in the lungs by in si tu hybridization. An unusual infiltration of neutrophils began before the p resence of exfoliated cells or Py replication and continued for 2-3 days an d 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, b oth the neutrophil infiltration and the transient hyperplasia are in stark contrast to the heavy macrophage infiltration that follows infection of lun gs with mouse adenovirus. Thus it appears that Py elicits a distinct host r esponse pattern not seen with other DNA viral infections. (C) 2000 academic Press.