Pathogenesis of SIV pneumonia: Selective replication of viral genotypes inthe lung

Lymphocytic interstitial pneumonia of HIV-infected individuals and SIV pneu monia of macaques are both characterized by diffuse Infiltration of the lun gs with lymphocytes, plasma cells, and macrophages. This study was undertak en to determine whether there are specific, macrophage-tropic genotypes tha t selectively replicate in the lung of macaques with SIV pneumonia, as In S IV encephalitis. Using a rapid, reproducible SIV/macaque model of AIDS, 11 pig-tailed macaques were intravenously inoculated with an immunosuppressive viral strain, SIV/DeltaB670, and a macrophage-tropic molecule clone, SIV/1 7E-Fr, and euthanized at 3 months postinoculation. All 11 macaques had seve re (6 macaques) or moderate (5 macaques) pneumonia. To identify the viral g enotypes that were replicating in the lung parenchyma, bronchoalveolar lava ge (BAL) cells, and peripheral blood mononuclear cells (PBMC) of each macaq ue, RNA was isolated and the SIV env V1 region was amplified, cloned, and s equenced. Lung homogenates and BAL cells contained a more limited repertoir e of viral genotypes than PBMC. SIV/17E-Fr was the major genotype In the lu ngs of 5 macaques and in BAL cells of 6 macaques. The remainder of the maca ques, had SIV/17E-Fr and the macrophage-tropic strains of SIV/DeltaB670 clo nes 2 and 12. In contrast, SIV/17E-Fr was the predominant strain in the PBM C of only 3 of 11 macaques. The viral strain that predominated in PBMC was rarely the strain that predominated in the lungs (only 3 of 11 macaques). T he severity of pulmonary lesions did not correlate with the levels of viral RNA in lung homogenates or In plasma. However, when only SIV/17E-Fr was ex pressed in the lung, the viral load in the lung was significantly higher (P =0.016) than when SIV/DeltaB670 was present alone or in combination with SI V/17E-Fr. These data suggest that SIV pneumonia is associated with selectiv e replication of specific macrophage-tropic genotypes in the lung and that SIV/17E-Fr has a selective advantage for replication in the lung. (C) 2001 Academic Press.