Bid regulates the pathogenesis of neurotropic reovirus.
Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-kappaB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsi...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000980&type=printable |
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| _version_ | 1841527142459899904 |
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| author | Pranav Danthi Andrea J Pruijssers Angela K Berger Geoffrey H Holm Sandra S Zinkel Terence S Dermody |
| author_facet | Pranav Danthi Andrea J Pruijssers Angela K Berger Geoffrey H Holm Sandra S Zinkel Terence S Dermody |
| author_sort | Pranav Danthi |
| collection | DOAJ |
| description | Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-kappaB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-kappaB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-kappaB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-kappaB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence. |
| format | Article |
| id | doaj-art-f14c2417fc3a4ca59aae9d41dca81321 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2010-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-f14c2417fc3a4ca59aae9d41dca813212025-01-16T05:31:02ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-07-016e100098010.1371/journal.ppat.1000980Bid regulates the pathogenesis of neurotropic reovirus.Pranav DanthiAndrea J PruijssersAngela K BergerGeoffrey H HolmSandra S ZinkelTerence S DermodyReovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-kappaB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-kappaB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-kappaB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-kappaB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000980&type=printable |
| spellingShingle | Pranav Danthi Andrea J Pruijssers Angela K Berger Geoffrey H Holm Sandra S Zinkel Terence S Dermody Bid regulates the pathogenesis of neurotropic reovirus. PLoS Pathogens |
| title | Bid regulates the pathogenesis of neurotropic reovirus. |
| title_full | Bid regulates the pathogenesis of neurotropic reovirus. |
| title_fullStr | Bid regulates the pathogenesis of neurotropic reovirus. |
| title_full_unstemmed | Bid regulates the pathogenesis of neurotropic reovirus. |
| title_short | Bid regulates the pathogenesis of neurotropic reovirus. |
| title_sort | bid regulates the pathogenesis of neurotropic reovirus |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000980&type=printable |
| work_keys_str_mv | AT pranavdanthi bidregulatesthepathogenesisofneurotropicreovirus AT andreajpruijssers bidregulatesthepathogenesisofneurotropicreovirus AT angelakberger bidregulatesthepathogenesisofneurotropicreovirus AT geoffreyhholm bidregulatesthepathogenesisofneurotropicreovirus AT sandraszinkel bidregulatesthepathogenesisofneurotropicreovirus AT terencesdermody bidregulatesthepathogenesisofneurotropicreovirus |