Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/19/2004
Publication Date: 12/8/2004
Citation: Miller, L.C., Fox, J.M. 2004. Apoptosis and porcine reproductive and respiratory syndrome virus. Veterinary Immunology and Immunopathology 102(3):131-142. Interpretive Summary: A feature of pigs infected with Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a delay in an immune response mounted against the virus infection. Recent studies in our laboratory and others have found that PRRSV does not trigger the innate immune response upon infection. In fact, it appears as though PRRSV actively suppresses activation of the innate immune response. Key activators of the innate immune response are also involved in activating cellular apoptosis, or cell suicide. This is a mechanism by which an infected cell can kill itself to spare the surrounding cells, tissues, and ultimately the animal. We have found that PRRSV infection does not result in direct induction of apoptosis. Thus, by a yet undetermined mechanism, PRRSV either prevents or simply does not induce the apoptotic pathway. Understanding the mechanisms of this finding will provide a more detailed understanding of PRRSV infection and may lead to novel intervention strategies to better manage the disease.
Technical Abstract: Despite numerous studies examining the possible induction of apoptosis in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) -infected cells, it remains unclear if PRRSV infection results in direct apoptotic induction. There is clear evidence that apoptotic cells are present in tissues from PRRSV-infected pigs. However, many of these studies have failed to show that the apoptotic cells are infected with PRRSV. This has led some investigators to propose that "bystander" cells, not infected cells, become apoptotic during PRRSV infection by a yet undetermined mechanism. Studies examining the induction of the apoptotic gene expression response to PRRSV infection are needed to determine if PRRSV replication triggers an apoptotic response. We have utilized microarray and semi-quantitative reverse-transcription polymerase chain reaction (sqRT-PCR) to evaluate apoptotic gene expression in PRRSV-infected MARC-145 cells. Twenty-six apoptosis-related genes were examined during the first 24 h of infection and found to be unaltered, indicating that apoptotic induction was not occurring in PRRSV-infected cells. Additionally, using detection of free nucleosomal complexes, we examined cells for both apoptotic and necrotic death resulting from PRRSV infection at varying multiplicities of infection. This study indicates that PRRSV-infected MARC-145 cells undergo necrosis at a much higher level than apoptosis, and increases with virus levels used to infect the cells.