title: Fas-mediated cytotoxicity induces degradation of vesicular stomatitis virus RNA transcripts and reduces viral titer.
abstract: Several investigators have recently examined the effect of Fas (CD95)-mediated apoptotic cell death on target cells (TC). The effect of Fas-mediated death on viral RNA within the TC, however, has not been explored. In this study, we investigated the ability of the Fas pathway to mediate pre-lytic degradation of vesicular stomatitis virus (VSV) RNA and TC RNA. We show that engagement of Fas antigen on VSV-infected Jurkat cells induces pre-lytic degradation of VSV RNA transcripts, whereas full-length VSV genome RNA, known to be tightly associated with viral proteins, is not degraded. Cellular RNA, including beta-actin and glyceraldehyde-3-phosphate-dehydrogenase mRNAs, is also degraded by Fas-mediated cytotoxicity. In addition, Fas-mediated cytotoxicity reduced the yield of VSV plaque-forming units (PFU) from Jurkat by an average of 82.0%. An anti-Fas blocking Ab inhibited the RNA degradation and restored the number of VSV PFU to near control levels. These data indicate that the Fas lytic pathway could play a role in the elimination of viruses through degradation of intracellular viral RNA. reserved
authors.affiliation: Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis 46202-5200, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Montel
authors.forename: G
authors.initials: G
authors.lastname: Hommel-Berrey
authors.forename: Z
authors.initials: Z
authors.lastname: Brahmi
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D014158:Transcription, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D019562:Viral Load; D019014:fas Receptor / Q000276:immunology*
chemical_list: D000199:Actins; D012333:RNA, Messenger; D012367:RNA, Viral; D019014:fas Receptor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases