Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase
Viruses manipulate cellular processes to create an environment favorable to replication. For most viruses, this includes subverting the expression of interferon (IFN), a signaling molecule that can stimulate production of a vast array of antiviral gene products. Rotavirus, a segmented double-strande...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2017-11-01
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| Series: | Microbial Cell |
| Subjects: | |
| Online Access: | http://microbialcell.com/researcharticles/shutdown-of-interferon-signaling-by-a-viral-hijacked-e3-ubiquitin-ligase/ |
| _version_ | 1811228220725395456 |
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| author | Kaitlin A. Davis John T. Patton |
| author_facet | Kaitlin A. Davis John T. Patton |
| author_sort | Kaitlin A. Davis |
| collection | DOAJ |
| description | Viruses manipulate cellular processes to create an environment favorable to replication. For most viruses, this includes subverting the expression of interferon (IFN), a signaling molecule that can stimulate production of a vast array of antiviral gene products. Rotavirus, a segmented double-stranded RNA virus that causes acute gastroenteritis in infants and young children, inhibits IFN expression through its nonstructural protein NSP1. This viral protein stifles IFN expression by inducing the degradation of host factors that are necessary for upregulating the activity of IFN genes. In the case of nearly all human and porcine rotavirus strains, NSP1 induces the ubiquitination-dependent proteasomal degradation of β-transducin repeat containing protein (β-TrCP), a host factor that plays an essential role in activating the IFN-transcription factor, NF-κB. Key to the process is the presence of a decoy sequence (degron) at the C-terminus of NSP1 that causes β-TrCP to mistakenly bind NSP1 instead of its natural target, inhibitor-of-κB (IκB). In a recent report published by Davis et al [2017; mBio 8(4): e01213-17], we describe molecular requirements that govern NSP1 recognition of β-TrCP, including an essential degron phosphorylation event, and the step-wise incorporation of NSP1 into hijacked cullin-RING E3 ligases (CRLs) that ubiquitinate and tag β-TrCP for degradation. Notably, although β-TrCP is chiefly recognized for its role as a master regulator of NF-κB signaling and IFN expression, β-TrCP also controls the stability of checkpoint proteins implicated in numerous other cellular pathways with antiviral activities, including autophagy and apoptosis. Thus, the impact of NSP1 on creating an intracellular environment favorable to virus replication may extend well beyond the IFN signaling pathway. |
| first_indexed | 2024-04-12T09:54:34Z |
| format | Article |
| id | doaj.art-aba1acf2127f438fbfdcefdb5f250b40 |
| institution | Directory Open Access Journal |
| issn | 2311-2638 |
| language | English |
| last_indexed | 2024-04-12T09:54:34Z |
| publishDate | 2017-11-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Microbial Cell |
| spelling | doaj.art-aba1acf2127f438fbfdcefdb5f250b402022-12-22T03:37:45ZengShared Science Publishers OGMicrobial Cell2311-26382017-11-0141138738910.15698/mic2017.11.600Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligaseKaitlin A. Davis0John T. Patton1Department of Biology, Johns Hopkins University, Baltimore, MD 21218.Department of Biology, Indiana University, Bloomington, IN 47405.Viruses manipulate cellular processes to create an environment favorable to replication. For most viruses, this includes subverting the expression of interferon (IFN), a signaling molecule that can stimulate production of a vast array of antiviral gene products. Rotavirus, a segmented double-stranded RNA virus that causes acute gastroenteritis in infants and young children, inhibits IFN expression through its nonstructural protein NSP1. This viral protein stifles IFN expression by inducing the degradation of host factors that are necessary for upregulating the activity of IFN genes. In the case of nearly all human and porcine rotavirus strains, NSP1 induces the ubiquitination-dependent proteasomal degradation of β-transducin repeat containing protein (β-TrCP), a host factor that plays an essential role in activating the IFN-transcription factor, NF-κB. Key to the process is the presence of a decoy sequence (degron) at the C-terminus of NSP1 that causes β-TrCP to mistakenly bind NSP1 instead of its natural target, inhibitor-of-κB (IκB). In a recent report published by Davis et al [2017; mBio 8(4): e01213-17], we describe molecular requirements that govern NSP1 recognition of β-TrCP, including an essential degron phosphorylation event, and the step-wise incorporation of NSP1 into hijacked cullin-RING E3 ligases (CRLs) that ubiquitinate and tag β-TrCP for degradation. Notably, although β-TrCP is chiefly recognized for its role as a master regulator of NF-κB signaling and IFN expression, β-TrCP also controls the stability of checkpoint proteins implicated in numerous other cellular pathways with antiviral activities, including autophagy and apoptosis. Thus, the impact of NSP1 on creating an intracellular environment favorable to virus replication may extend well beyond the IFN signaling pathway.http://microbialcell.com/researcharticles/shutdown-of-interferon-signaling-by-a-viral-hijacked-e3-ubiquitin-ligase/rotavirusinterferonubiquitinE3 ligaseβ-TrCP |
| spellingShingle | Kaitlin A. Davis John T. Patton Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase Microbial Cell rotavirus interferon ubiquitin E3 ligase β-TrCP |
| title | Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase |
| title_full | Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase |
| title_fullStr | Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase |
| title_full_unstemmed | Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase |
| title_short | Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase |
| title_sort | shutdown of interferon signaling by a viral hijacked e3 ubiquitin ligase |
| topic | rotavirus interferon ubiquitin E3 ligase β-TrCP |
| url | http://microbialcell.com/researcharticles/shutdown-of-interferon-signaling-by-a-viral-hijacked-e3-ubiquitin-ligase/ |
| work_keys_str_mv | AT kaitlinadavis shutdownofinterferonsignalingbyaviralhijackede3ubiquitinligase AT johntpatton shutdownofinterferonsignalingbyaviralhijackede3ubiquitinligase |