Porcine reproductive and respiratory syndrome virus modulates apoptosis during replication in alveolar macrophages.
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.
Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium. sarah.costers@ugent.be
Sarah
S
Costers
David J
DJ
Lefebvre
Peter L
PL
Delputte
Hans J
HJ
Nauwynck
D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000473:pathology; D019316:Porcine respiratory and reproductive syndrome virus / Q000472:pathogenicity*; D019311:Staurosporine / Q000494:pharmacology; D013553:Swine Diseases / Q000473:pathology / Q000821:virology; D014779:Virus Replication / Q000502:physiology*
D019311:Staurosporine