PMID- 18563285 OWN - NLM STAT- MEDLINE DCOM- 20081218 LR - 20131121 IS - 0304-8608 (Print) IS - 0304-8608 (Linking) VI - 153 IP - 8 DP - 2008 TI - Porcine reproductive and respiratory syndrome virus modulates apoptosis during replication in alveolar macrophages. PG - 1453-65 LID - 10.1007/s00705-008-0135-5 [doi] AB - Different viruses have evolved strategies that inhibit apoptosis of the host cell early in infection and/or induce apoptosis in the host cell late in infection. In this study, it was investigated if and when porcine reproductive and respiratory syndrome virus (PRRSV) modulates apoptosis in PRRSV-infected macrophages. The PRRSV replication cycle in macrophages was completed within 12 h post-inoculation (hpi). PRRSV-infected macrophages, treated with staurosporine at 4, 5, 6 and 8 hpi, were significantly protected against staurosporine-induced apoptosis, but PRRSV-infected macrophages, treated with staurosporine at 12 hpi, were not. In contrast, starting from 12 hpi, all PRRSV-infected macrophages died by caspase-dependent apoptosis, which culminated in secondary necrosis. Treatment of PRRSV-infected macrophages with Z-Val-DL-Asp-fluoromethylketone indicated that apoptosis late in infection was not essential for efficient virus release. Anti- and pro-apoptotic activities were also observed in PRRSV-infected Marc-145 cells. In conclusion, this study shows that PRRSV stimulates anti-apoptotic pathways in macrophages early in infection and that PRRSV-infected macrophages die by apoptosis late in infection. FAU - Costers, Sarah AU - Costers S AD - Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium. sarah.costers@ugent.be FAU - Lefebvre, David J AU - Lefebvre DJ FAU - Delputte, Peter L AU - Delputte PL FAU - Nauwynck, Hans J AU - Nauwynck HJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080619 PL - Austria TA - Arch Virol JT - Archives of virology JID - 7506870 RN - H88EPA0A3N (Staurosporine) SB - IM MH - Animals MH - Apoptosis/immunology/*physiology MH - Macrophages, Alveolar/drug effects/immunology/*virology MH - Porcine Reproductive and Respiratory Syndrome/*immunology/pathology MH - Porcine respiratory and reproductive syndrome virus/*pathogenicity MH - Staurosporine/pharmacology MH - Swine Diseases/pathology/virology MH - Virus Replication/*physiology EDAT- 2008/06/20 09:00 MHDA- 2008/12/19 09:00 CRDT- 2008/06/20 09:00 PHST- 2008/04/03 00:00 [received] PHST- 2008/05/10 00:00 [accepted] PHST- 2008/06/20 09:00 [pubmed] PHST- 2008/12/19 09:00 [medline] PHST- 2008/06/20 09:00 [entrez] AID - 10.1007/s00705-008-0135-5 [doi] PST - ppublish SO - Arch Virol. 2008;153(8):1453-65. doi: 10.1007/s00705-008-0135-5. Epub 2008 Jun 19.