Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells
Copyright © 2015 Elsevier Inc. All rights reserved..
Lloviu virus (LLOV) is a new member of the filovirus family that also includes Ebola virus (EBOV) and Marburg virus (MARV). LLOV has not been cultured; however, its genomic RNA sequence indicates the coding capacity to produce homologs of the EBOV and MARV VP24, VP35, and VP40 proteins. EBOV and MARV VP35 proteins inhibit interferon (IFN)-alpha/beta production and EBOV VP35 blocks activation of the antiviral kinase PKR. The EBOV VP24 and MARV VP40 proteins inhibit IFN signaling, albeit by different mechanisms. Here we demonstrate that LLOV VP35 suppresses Sendai virus induced IFN regulatory factor 3 (IRF3) phosphorylation, IFN-α/β production, and PKR phosphorylation. Additionally, LLOV VP24 blocks tyrosine phosphorylated STAT1 binding to karyopherin alpha 5 (KPNA5), STAT1 nuclear accumulation, and IFN-induced gene expression. LLOV VP40 lacks detectable IFN antagonist function. These activities parallel EBOV IFN inhibitory functions. EBOV and LLOV VP35 and VP24 proteins also inhibit IFN responses in bat cells. These data suggest that LLOV infection will block innate immune responses in a manner similar to EBOV.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:485 |
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| Enthalten in: |
Virology - 485(2015) vom: 23. Nov., Seite 145-52 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Feagins, Alicia R [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.01.2016 Date Revised 22.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.virol.2015.07.010 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM251655903 |
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| 100 | 1 | |a Feagins, Alicia R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells |
| 264 | 1 | |c 2015 | |
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| 500 | |a Date Completed 27.01.2016 | ||
| 500 | |a Date Revised 22.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 Elsevier Inc. All rights reserved. | ||
| 520 | |a Lloviu virus (LLOV) is a new member of the filovirus family that also includes Ebola virus (EBOV) and Marburg virus (MARV). LLOV has not been cultured; however, its genomic RNA sequence indicates the coding capacity to produce homologs of the EBOV and MARV VP24, VP35, and VP40 proteins. EBOV and MARV VP35 proteins inhibit interferon (IFN)-alpha/beta production and EBOV VP35 blocks activation of the antiviral kinase PKR. The EBOV VP24 and MARV VP40 proteins inhibit IFN signaling, albeit by different mechanisms. Here we demonstrate that LLOV VP35 suppresses Sendai virus induced IFN regulatory factor 3 (IRF3) phosphorylation, IFN-α/β production, and PKR phosphorylation. Additionally, LLOV VP24 blocks tyrosine phosphorylated STAT1 binding to karyopherin alpha 5 (KPNA5), STAT1 nuclear accumulation, and IFN-induced gene expression. LLOV VP40 lacks detectable IFN antagonist function. These activities parallel EBOV IFN inhibitory functions. EBOV and LLOV VP35 and VP24 proteins also inhibit IFN responses in bat cells. These data suggest that LLOV infection will block innate immune responses in a manner similar to EBOV | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Filovirus | |
| 650 | 4 | |a Innate immune response | |
| 650 | 4 | |a Interferon | |
| 650 | 4 | |a Interferon antagonist | |
| 650 | 4 | |a Lloviu virus | |
| 650 | 7 | |a IRF3 protein, human |2 NLM | |
| 650 | 7 | |a Interferon Regulatory Factor-3 |2 NLM | |
| 650 | 7 | |a Interferon-alpha |2 NLM | |
| 650 | 7 | |a KPNA5 protein, human |2 NLM | |
| 650 | 7 | |a STAT1 Transcription Factor |2 NLM | |
| 650 | 7 | |a STAT1 protein, human |2 NLM | |
| 650 | 7 | |a VP24 protein, Ebola virus |2 NLM | |
| 650 | 7 | |a VP35 protein, filovirus |2 NLM | |
| 650 | 7 | |a VP40 protein, virus |2 NLM | |
| 650 | 7 | |a Viral Matrix Proteins |2 NLM | |
| 650 | 7 | |a Viral Proteins |2 NLM | |
| 650 | 7 | |a Viral Regulatory and Accessory Proteins |2 NLM | |
| 650 | 7 | |a alpha Karyopherins |2 NLM | |
| 650 | 7 | |a Interferon-beta |2 NLM | |
| 650 | 7 | |a 77238-31-4 |2 NLM | |
| 650 | 7 | |a eIF-2 Kinase |2 NLM | |
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| 700 | 1 | |a Basler, Christopher F |e verfasserin |4 aut | |
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