Figure 1.

Herpesviral infections change the nature of the inflammatory response to subsequent fibrotic stimuli. Mice were given 5 × 10⁴ pfu MHV-68 or saline 14 days prior to the instillation of bleomycin as a fibrotic stimulus. Mice were euthanized and lungs were prepared for histology 21 days post-bleomycin. Panels on the left-hand side represent mice pre-treated with saline, and then challenged with bleomcyin. Panels on the right-hand side represent mice infected with MHV-68 prior to the bleomcyin challenge. MHV-68 was latent at the time of bleomycin inoculation. Viral pre-infection causes increased numbers of inflammatory cells to enter the lung during the subsequent fibrotic response. We have verified this with collagenase digests and cell counts as well (not shown). It is particularly interesting that the virally infected mice show focal clusters of mononuclear cells (yellow arrows) that are not seen in the mice challenged with bleomycin alone. The inset in the lower right panel is a 1,000× magnification of one of these mononuclear foci. Based on morphology, these cells are likely leukocytes.