Apoptosis induced in vivo during acute infection by porcine reproductive and respiratory syndrome virus

We studied apoptosis caused by porcine reproductive and respiratory syndrom e virus (PRRSV) in vivo, focusing on the tissues that constitute the main t argets for infection: lung and lymphoid tissues. Previous investigators hav e shown that the PRRSV glycoprotein p25, encoded by PRRSV open reading fram e 5, induces apoptosis when expressed in COS-1 cells. Results of studies co nducted in our laboratory indicate the simultaneous occurrence of PRRSV-ind uced alterations of spermatogenesis and apoptotic death of germinal epithel ial cells in the testicle. In this study, the goal was to determine whether virus-induced apoptosis is a direct mechanism of cell death caused by PRRS V in infected pigs. Eight 3-week-old pigs were intranasally inoculated with PRRSV 16244B, a highly virulent field strain. Lung, tonsil, bronchial lymp h node, spleen, and heart were assessed histologically at 4 and 7 days post infection. To characterize PRRSV-infected cells and apoptotic cell death, w e used immunohistochemical methods for detection of viral antigen, DNA elec trophoresis for detection of DNA fragmentation, the terminal deoxynucleotid yl transferase-mediated deoxyuridine triphosphate-fluorescein nick end labe ling method for in situ detection of DNA strand breaks, and electron micros copy for ultrastructural morphologic studies. PRRSV infection resulted in w idespread apoptosis in the lungs and lymphoid tissues of infected pigs. Vir us infection-induced apoptotic cells were more abundant than PRRSV-infected cells in all tissues. DNA laddering was detected in lung and lymphoid tiss ues. However, double-labeling experiments demonstrated that the majority of apoptotic cells did not colocalize with PRRSV-infected cells. Our findings suggest the presence of an indirect mechanism in the induction of apoptosi s for PRRSV.