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Title: Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells

Abstract

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. - Highlights: • Lloviu virus (LLOV) is a new member of the filovirus family. • LLOV VP35 blocks IRF3 phosphorylation, IFN-α/β production and PKR phosphorylation. • LLOV VP24 inhibits IFN responses by targetingmore » phospho-STAT1 KPNA interaction. • Infection by LLOV may block innate immune responses in a manner similar to EBOV.« less

Authors:
;
Publication Date:
OSTI Identifier:
22581647
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 485; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BATS; GENES; INTERFERON; PHOSPHORYLATION; RNA; TYROSINE; VIRUSES

Citation Formats

Feagins, Alicia R., and Basler, Christopher F., E-mail: chris.basler@mssm.edu. Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells. United States: N. p., 2015. Web. doi:10.1016/J.VIROL.2015.07.010.
Feagins, Alicia R., & Basler, Christopher F., E-mail: chris.basler@mssm.edu. Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells. United States. doi:10.1016/J.VIROL.2015.07.010.
Feagins, Alicia R., and Basler, Christopher F., E-mail: chris.basler@mssm.edu. Sun . "Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells". United States. doi:10.1016/J.VIROL.2015.07.010.
@article{osti_22581647,
title = {Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells},
author = {Feagins, Alicia R. and Basler, Christopher F., E-mail: chris.basler@mssm.edu},
abstractNote = {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. - Highlights: • Lloviu virus (LLOV) is a new member of the filovirus family. • LLOV VP35 blocks IRF3 phosphorylation, IFN-α/β production and PKR phosphorylation. • LLOV VP24 inhibits IFN responses by targeting phospho-STAT1 KPNA interaction. • Infection by LLOV may block innate immune responses in a manner similar to EBOV.},
doi = {10.1016/J.VIROL.2015.07.010},
journal = {Virology},
issn = {0042-6822},
number = ,
volume = 485,
place = {United States},
year = {2015},
month = {11}
}