Pathogenesis of simian immunodeficiency virus pneumonia: an immunopathological response to virus

Abstract

Although many human immunodeficiency virus-infected individuals develop lymphocytic interstitial pneumonia, the roles of host and viral factors in the pathogenesis of pneumonia are not well defined. Human immunodeficiency virus-infected children with lymphocytic interstitial pneumonia have human immunodeficiency virus-specific cytotoxic T cells in pulmonary infiltrates, increased survival time, and a reduced incidence of opportunistic infections, suggesting that lymphocytic interstitial pneumonia may reflect an effective antiviral immune response. In this study, 20 macaques were inoculated with related macrophage-tropic simian immunodeficiency viruses and examined for pulmonary lesions and virus gene expression. Ten macaques developed moderate to severe pneumonia characterized by perivascular, peribronchial, and interstitial infiltrates of lymphocytes and macrophages. Large numbers of pulmonary cytotoxic lymphocytes were demonstrated in macaques with moderate to severe pneumonia (P < 0.05) by immunostaining for TIA-1. There was no difference in viral load between macaques with moderate to severe pneumonia and those with mild to no pulmonary lesions. In five macaques inoculated with the same virus swarm, there was a significant (P < 0.05) inverse correlation between the percentage decline in CD4+ T-cell counts and the severity of pulmonary lesions. Pulmonary infiltrates of cytotoxic lymphocytes, the lack of correlation between severity of pulmonary lesions and virus gene expression, and the inverse relationship between pneumonia and inmune status suggest that simian immunodeficiency virus pneumonia may represent an immunopathological response to macrophage-tropic virus.

Figure 1.

a: Pulmonary lesions in SIV-inoculated macaques are characterized by perivascular and interstitial infiltrates of lymphocytes and macrophages. Macaque 14E, H&E, magnification ×100. b: Immunohistochemical staining for TIA-1, a cytotoxic granule marker, detects high numbers of positive cells in the pulmonary interstitial inflammatory infiltrate. Macaque 14E, nuclear fast red counterstain, magnification ×200. c: Double immunolabeling demonstrates that cells staining for TIA-1 (blue; arrowheads) are distinct from pulmonary macrophages identified by an anti-CD68 monoclonal antibody (red; arrows). Magnification ×200. d: In situ hybridization for viral RNA showing an occasional positive cell (arrow) amid numerous inflammatory cells. Macaque 14E, nuclear fast red counterstain, magnification ×200. e: Double labeling consisting of immunohistochemical staining for the macrophage marker ferritin (brown) and in situ hybridization for viral RNA (blue) shows a macrophage containing viral mRNA. Macaque 14E, nuclear fast red counterstain, magnification ×500.