Apoptosis Induced In Vivo During Acute Infection by Porcine Reproductive and Respiratory Syndrome Virus

Abstract

We studied apoptosis caused by porcine reproductive and respiratory syndrome virus (PRRSV) in vivo, focusing on the tissues that constitute the main targets for infection: lung and lymphoid tissues. Previous investigators have shown that the PRRSV glycoprotein p25, encoded by PRRSV open reading frame 5, induces apoptosis when expressed in COS-1 cells. Results of studies conducted in our laboratory indicate the simultaneous occurrence of PRRSV-induced alterations of spermatogenesis and apoptotic death of germinal epithelial 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 PRRSV in infected pigs. Eight 3-week-old pigs were intranasally inoculated with PRRSV 16244B, a highly virulent field strain. Lung, tonsil, bronchial lymph node, spleen, and heart were assessed histologically at 4 and 7 days postinfection. To characterize PRRSV-infected cells and apoptotic cell death, we used immunohistochemical methods for detection of viral antigen, DNA electrophoresis for detection of DNA fragmentation, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-fluorescein nick end labeling method for in situ detection of DNA strand breaks, and electron microscopy for ultrastructural morphologic studies. PRRSV infection resulted in widespread apoptosis in the lungs and lymphoid tissues of infected pigs. Virus infection-induced apoptotic cells were more abundant than PRRSV-infected cells in all tissues. DNA laddering was detected in lung and lymphoid tissues. 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 apoptosis for PRRSV.

Apoptosis in the lungs of pigs infected with porcine reproductive and respiratory syndrome virus and associations with the production of apoptogenic cytokines

“…Apoptosis occurred both in virus-infected and in non-infected cells. Most apoptotic cells were noninfected, which is in agreement with previous studies [7,24,27].…”

“…On a morphological basis, the apoptotic cells are assumed to be alveolar and pulmonary intravascular macrophages and mononuclear cells in the alveolar septa. Doublelabelling experiments indicate that most apoptotic cells are non-infected [24,27].…”

“…Recently, it has been demonstrated that the porcine reproductive and respiratory syndrome virus (PRRSV) induces apoptosis in the lungs [7,17,24,27]. On a morphological basis, the apoptotic cells are assumed to be alveolar and pulmonary intravascular macrophages and mononuclear cells in the alveolar septa.…”

Apoptosis Induced In Vitro and In Vivo During Infection by Ebola and Marburg Viruses

“…Cells undergoing necrosis as a result of the cytopathogenic effect of filoviral replication included cells of the MPS, hepatocytes, fibroblasts, FRC, and endothelial cells, but apoptosis affected only lymphocytes. Apoptosis of lymphocytes is not unique to filoviruses; it has also been reported independent of viral replication in HIV and SIV infections (Finkel et al, 1995), African swine fever virus infections (Carrasco et al, 1996;Oura et al, 1998), and porcine reproductive and respiratory syndrome virus infections (Sur et al, 1998).…”

“…Necrosis, in contrast, is characterized by rapid enlargement of cells and damage to organelles and plasma membrane leading to cell lysis and an inflammatory response. A number of viruses induce apoptosis either directly (Lewis et al, 1996;Oberhaus et al, 1997) or indirectly (Carrasco et al, 1996;Finkel et al, 1995;Sur et al, 1998). In general, the molecular pathways by which viruses induce apoptosis are not well understood.…”