Alveolitis induced by influenza virus.
Previous studies of influenza virus infections have focused on the acute pathologic manifestations associated with the virus pneumonia; however, there is evidence suggestive of persistent pathologic processes with possible long-term consequences. Herein we have examined the long-term outcome of virus pneumonia in mice infected by aerosol inhalation of a sublethal dose of influenza A/PR8/34 virus. At 3, 5, 7, 9, 15, 30, 60, 90, 120 days, and a year thereafter, the lavageable lung cell populations and differential counts were quantitated. Consistent with previous studies we demonstrated an inflammatory cellular response during the acute phase of the infection. However, this inflammatory response did not completely resolve, the pulmonary leukocytosis remaining stable from Day 30 through a year after virus infection. For example, on Day 30, virus-infected lungs yielded 12.4 +/- 0.9 X 10(5) cells per lavage of which 15 +/- 3% were polymorphonuclear leukocytes, 18 +/- 4% were lymphocytes, and 67 +/- 5% were alveolar macrophages. In contrast, 7.2 +/- 0.5 X 10(5) cells per lavage were obtained from uninfected lungs of which more than 98% were alveolar macrophages. Histopathologic examination of virus-infected lungs showed an ongoing inflammatory response resulting in patchy mononuclear interstitial pneumonia, deposition of collagen in the affected areas, and marked hyperplasia of bronchial-associated lymphoid tissue. Infectious virus could not be recovered after Day 9. However, in contrast to loss of infectivity, viral antigen persisted at high concentrations in the lung. We conclude that influenza virus infection induced a long-term alveolitis that is associated with persistence of viral antigen. These data open the possibility that influenza virus infections may play a role in interstitial lung disease.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D005260:Female; D007249:Inflammation; D009980:Influenza A virus / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology*; D011024:Pneumonia, Viral / Q000276:immunology / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000473:pathology
D000956:Antigens, Viral