Apoptosis correlates with immune activation in intestinal lymphoid tissue from macaques acutely infected by a highly enteropathic simian immunodeficiency virus, SIVsmmPBj14.

The PBj14 isolate of simian immunodeficiency virus, SIVsmmPBj14, induces an acutely lethal disease in experimentally inoculated pigtailed macaques, that is characterized by severe enteropathy and extensive immune activation, particularly within gut-associated lymphoid tissue (GALT). Experiments were conducted to determine whether virally induced immune activation might promote the induction of apoptosis in GALT during acute SIVsmmPBj14 infection. In situ labeling studies revealed a significant increase in the number of apoptotic cells within GALT from macaques with acute SIVsmmPBj14 infection, compared to (i) other tissues from the same animals, (ii) GALT from virus-negative animals, or (iii) GALT from macaques that were sacrificed soon after infection with SIVmac239, which does not cause acutely lethal enteropathy. These findings were confirmed by biochemical assays of DNA fragmentation, using DNA laddering and ELISA techniques. Immunostaining experiments revealed a strong positive correlation between the extent of apoptosis and the degree of immune activation, as assessed either by the number of cells which contained nuclear (activated) RelA or by the number of cells immunoreactive for CD25, a T-cell activation marker. Additional analyses of SIV antigen expression revealed that the majority of the apoptotic cells were not productively infected by SIV (i.e., that they were bystander cells). Taken together, these findings support the hypothesis that SIVsmmPBj14 efficiently induces immune activation and that this results in extensive apoptosis within gut-associated lymphoid tissue during acute viral infection.