PMID- 26962215
OWN - NLM
STAT- MEDLINE
DCOM- 20170426
LR  - 20201209
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 10
DP  - 2016 May 15
TI  - Effects of Filovirus Interferon Antagonists on Responses of Human 
      Monocyte-Derived Dendritic Cells to RNA Virus Infection.
PG  - 5108-5118
LID - 10.1128/JVI.00191-16 [doi]
AB  - Dendritic cells (DCs) are major targets of filovirus infection in vivo Previous 
      studies have shown that the filoviruses Ebola virus (EBOV) and Marburg virus 
      (MARV) suppress DC maturation in vitro Both viruses also encode innate immune 
      evasion functions. The EBOV VP35 (eVP35) and the MARV VP35 (mVP35) proteins each 
      can block RIG-I-like receptor signaling and alpha/beta interferon (IFN-alpha/beta) 
      production. The EBOV VP24 (eVP24) and MARV VP40 (mVP40) proteins each inhibit the 
      production of IFN-stimulated genes (ISGs) by blocking Jak-STAT signaling; 
      however, this occurs by different mechanisms, with eVP24 blocking nuclear import 
      of tyrosine-phosphorylated STAT1 and mVP40 blocking Jak1 function. MARV VP24 
      (mVP24) has been demonstrated to modulate host cell antioxidant responses. 
      Previous studies demonstrated that eVP35 is sufficient to strongly impair primary 
      human monocyte-derived DC (MDDC) responses upon stimulation induced through the 
      RIG-I-like receptor pathways. We demonstrate that mVP35, like eVP35, suppresses 
      not only IFN-alpha/beta production but also proinflammatory responses after stimulation 
      of MDDCs with RIG-I activators. In contrast, eVP24 and mVP40, despite suppressing 
      ISG production upon RIG-I activation, failed to block upregulation of maturation 
      markers or T cell activation. mVP24, although able to stimulate expression of 
      antioxidant response genes, had no measurable impact of DC function. These data 
      are consistent with a model where filoviral VP35 proteins are the major 
      suppressors of DC maturation during filovirus infection, whereas the filoviral 
      VP24 proteins and mVP40 are insufficient to prevent DC maturation. IMPORTANCE: 
      The ability to suppress the function of dendritic cells (DCs) likely contributes 
      to the pathogenesis of disease caused by the filoviruses Ebola virus and Marburg 
      virus. To clarify the basis for this DC suppression, we assessed the effect of 
      filovirus proteins known to antagonize innate immune signaling pathways, 
      including Ebola virus VP35 and VP24 and Marburg virus VP35, VP40, and VP24, on DC 
      maturation and function. The data demonstrate that the VP35s from Ebola virus and 
      Marburg virus are the major suppressors of DC maturation and that the effects on 
      DCs of the remaining innate immune inhibitors are minor.
CI  - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved.
FAU - Yen, Benjamin C
AU  - Yen BC
AD  - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, 
      New York, USA.
FAU - Basler, Christopher F
AU  - Basler CF
AD  - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, 
      New York, USA cbasler@gsu.edu.
LA  - eng
GR  - R01 AI059536/AI/NIAID NIH HHS/United States
GR  - U19 AI109945/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20160429
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Interferon-alpha)
RN  - 0 (Nucleocapsid Proteins)
RN  - 0 (Nucleoproteins)
RN  - 0 (VP24 protein, Marburg virus)
RN  - 0 (VP35 protein, filovirus)
RN  - 0 (Viral Core Proteins)
RN  - 0 (Viral Proteins)
RN  - 0 (Viral Regulatory and Accessory Proteins)
RN  - 0 (nucleoprotein VP35, Ebola virus)
RN  - 77238-31-4 (Interferon-beta)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Cell Differentiation
MH  - Dendritic Cells/*physiology/*virology
MH  - Ebolavirus/*chemistry
MH  - Encephalomyocarditis virus/physiology
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Interferon-alpha/genetics/immunology
MH  - Interferon-beta/genetics/immunology
MH  - Interferon-gamma/metabolism
MH  - Marburgvirus/*chemistry
MH  - Nucleocapsid Proteins
MH  - Nucleoproteins/genetics/physiology
MH  - RNA Viruses/*physiology
MH  - Sendai virus/physiology
MH  - Transduction, Genetic
MH  - Viral Core Proteins/genetics/physiology
MH  - Viral Proteins/genetics/*physiology
MH  - Viral Regulatory and Accessory Proteins/*physiology
PMC - PMC4859717
EDAT- 2016/03/11 06:00
MHDA- 2017/04/27 06:00
PMCR- 2016/10/29
CRDT- 2016/03/11 06:00
PHST- 2016/01/29 00:00 [received]
PHST- 2016/03/06 00:00 [accepted]
PHST- 2016/03/11 06:00 [entrez]
PHST- 2016/03/11 06:00 [pubmed]
PHST- 2017/04/27 06:00 [medline]
PHST- 2016/10/29 00:00 [pmc-release]
AID - JVI.00191-16 [pii]
AID - 00191-16 [pii]
AID - 10.1128/JVI.00191-16 [doi]
PST - epublish
SO  - J Virol. 2016 Apr 29;90(10):5108-5118. doi: 10.1128/JVI.00191-16. Print 2016 May 
      15.