title: Intrinsic apoptotic pathway is subverted in mouse macrophages persistently infected by RSV.
abstract: To persist, a virus must co-exist with the host that it infects, thus allowing the virus to survive and to subvert the programmed cell death of the host. In this study, we investigated whether the intrinsic pathway of the apoptotic process is suppressed in a previously reported macrophage cell line persistently infected with respiratory syncytial virus (RSV). To this end, after using staurosporine to induce apoptosis, we determined cell viability and the degree of annexin staining and DNA fragmentation between infected and mock-infected cells. RSV persistence leads to a subversion of apoptosis; whereas in mock-infected macrophages, apoptosis was evident. The cellular apoptotic pathway involve was searched by determining the activities of caspases and the expression of anti-apoptotic proteins. Although caspases-3 and -9 were expressed, their activities were altered; the activity of caspase-3 was reduced and that of caspase-9 could not be detected. Expression of anti-apoptotic proteins Bcl-2, Bcl-X, and XIAP was enhanced, with Bcl-X and XIAP being regulated post-transcriptionally; the induction of the anti-apoptotic factors and the reduced caspases activities might account for the subversion of apoptosis. The data implies that in our viral persistence model an anti-apoptotic program is induced relating alterations of caspases-3 and -9 activity and expression of anti-apoptotic proteins, suggesting that the intrinsic pathway is suppressed. These findings are of importance for understanding the intracellular genes involved in subversion of apoptosis by RSV persistence in macrophages.
authors: Laboratory of Virology, Department of Microbiology and Parasitology, Faculty of Medicine, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, D.F. 04510, Mexico. ynakamura@cinvestav.mx
authors: Yuko
authors: Y
authors: Nakamura-López
authors: Nicolas
authors: N
authors: Villegas-Sepúlveda
authors: Rosa Elena
authors: RE
authors: Sarmiento-Silva
authors: Beatriz
authors: B
authors: Gómez
mesh_terms: D000818:Animals; D017302:Annexins / Q000032:analysis; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D057131:Immune Evasion; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D051379:Mice; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000472:pathogenicity*; D019311:Staurosporine / Q000633:toxicity; D015854:Up-Regulation
chemical_list: D017302:Annexins; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D053453:Caspase 9; D019311:Staurosporine