Langat virus inhibits the gp130/JAK/STAT signaling by reducing the gp130 protein level
© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA..
The tick-borne encephalitis virus (TBEV) serocomplex includes several medically important flavivirus members endemic to Europe, Asia, and North America, which can induce severe neuroinvasive or viscerotropic diseases with unclear mechanisms of pathogenesis. Langat virus (LGTV) shares a high sequence identity with TBEV but exhibits lower pathogenic potential in humans and serves as a model for virus-host interactions. In this study, we demonstrated that LGTV infection inhibits the activation of gp130/JAK/STAT (Janus kinases (JAK) and signal transducer and activator of transcription (STAT)) signaling, which plays a pivotal role in numerous biological processes. Our data show that the LGTV-infected cells had significantly lower phosphorylated STAT3 (pSTAT3) protein upon oncostatin M (OSM) stimulation than the mock-infected control. LGTV infection blocked the nuclear translocation of STAT3 without a significant effect on total STAT3 protein level. LGTV inhibited JAK1 activation and reduced gp130 protein expression in infected cells, with the viral NS5 protein mediating this effect. TBEV infection also reduces gp130 level. On the other hand, pretreatment of Vero cells with OSM significantly reduces LGTV replication, and STAT1/STAT2 knockdown had little effect on OSM-mediated antiviral effect, which suggests it is independent of STAT1/STAT2 and, instead, it is potentially mediated by STAT3 signlaing. These findings shed light on the LGTV and TBEV-cell interactions, offering insights for the future development of antiviral therapeutics and improved vaccines.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
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| Enthalten in: |
Journal of medical virology - 96(2024), 4 vom: 31. März, Seite e29522 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lin, Shaoli [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.03.2024 Date Revised 28.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jmv.29522 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. | ||
| 520 | |a The tick-borne encephalitis virus (TBEV) serocomplex includes several medically important flavivirus members endemic to Europe, Asia, and North America, which can induce severe neuroinvasive or viscerotropic diseases with unclear mechanisms of pathogenesis. Langat virus (LGTV) shares a high sequence identity with TBEV but exhibits lower pathogenic potential in humans and serves as a model for virus-host interactions. In this study, we demonstrated that LGTV infection inhibits the activation of gp130/JAK/STAT (Janus kinases (JAK) and signal transducer and activator of transcription (STAT)) signaling, which plays a pivotal role in numerous biological processes. Our data show that the LGTV-infected cells had significantly lower phosphorylated STAT3 (pSTAT3) protein upon oncostatin M (OSM) stimulation than the mock-infected control. LGTV infection blocked the nuclear translocation of STAT3 without a significant effect on total STAT3 protein level. LGTV inhibited JAK1 activation and reduced gp130 protein expression in infected cells, with the viral NS5 protein mediating this effect. TBEV infection also reduces gp130 level. On the other hand, pretreatment of Vero cells with OSM significantly reduces LGTV replication, and STAT1/STAT2 knockdown had little effect on OSM-mediated antiviral effect, which suggests it is independent of STAT1/STAT2 and, instead, it is potentially mediated by STAT3 signlaing. These findings shed light on the LGTV and TBEV-cell interactions, offering insights for the future development of antiviral therapeutics and improved vaccines | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a JAK/STAT signaling | |
| 650 | 4 | |a Langat virus (LGTV) | |
| 650 | 4 | |a NS5 | |
| 650 | 4 | |a gp130 | |
| 650 | 4 | |a signal transducer and activator of transcription 3 (STAT3) | |
| 650 | 4 | |a tick‐borne encephalitis virus (TBEV) | |
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| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 700 | 1 | |a Wang, Xiaochun |e verfasserin |4 aut | |
| 700 | 1 | |a Sallapalli, Bhargava Teja |e verfasserin |4 aut | |
| 700 | 1 | |a Hage, Adam |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Peixi |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Best, Sonja M |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanjin |e verfasserin |4 aut | |
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