Mutual antagonism between the ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome

Priya Luthra, Parameshwaran Ramanan, Chad Mire, Carla Weisend, Yoshimi Tsuda, Benjamin Yen, Gai Liu, Daisy W. Leung, Thomas Geisbert, Hideki Ebihara, Gaya K. Amarasinghe, Christopher F. Basler

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection.

Original languageEnglish (US)
Pages (from-to)74-84
Number of pages11
JournalCell Host and Microbe
Volume14
Issue number1
DOIs
StatePublished - Jul 17 2013

Fingerprint

Ebolavirus
Viral RNA
Ebola Hemorrhagic Fever
Pattern Recognition Receptors
Virus Replication
Infection
Antiviral Agents
Adenosine Triphosphatases
Carrier Proteins
Viruses
Proteins
filovirus VP35 protein
Ebola virus nucleoprotein VP35

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Mutual antagonism between the ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome. / Luthra, Priya; Ramanan, Parameshwaran; Mire, Chad; Weisend, Carla; Tsuda, Yoshimi; Yen, Benjamin; Liu, Gai; Leung, Daisy W.; Geisbert, Thomas; Ebihara, Hideki; Amarasinghe, Gaya K.; Basler, Christopher F.

In: Cell Host and Microbe, Vol. 14, No. 1, 17.07.2013, p. 74-84.

Research output: Contribution to journalArticle

Luthra, P, Ramanan, P, Mire, C, Weisend, C, Tsuda, Y, Yen, B, Liu, G, Leung, DW, Geisbert, T, Ebihara, H, Amarasinghe, GK & Basler, CF 2013, 'Mutual antagonism between the ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome', Cell Host and Microbe, vol. 14, no. 1, pp. 74-84. https://doi.org/10.1016/j.chom.2013.06.010
Luthra, Priya ; Ramanan, Parameshwaran ; Mire, Chad ; Weisend, Carla ; Tsuda, Yoshimi ; Yen, Benjamin ; Liu, Gai ; Leung, Daisy W. ; Geisbert, Thomas ; Ebihara, Hideki ; Amarasinghe, Gaya K. ; Basler, Christopher F. / Mutual antagonism between the ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome. In: Cell Host and Microbe. 2013 ; Vol. 14, No. 1. pp. 74-84.
@article{6bcca6767c6d4906b907e503601f6645,
title = "Mutual antagonism between the ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome",
abstract = "The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection.",
author = "Priya Luthra and Parameshwaran Ramanan and Chad Mire and Carla Weisend and Yoshimi Tsuda and Benjamin Yen and Gai Liu and Leung, {Daisy W.} and Thomas Geisbert and Hideki Ebihara and Amarasinghe, {Gaya K.} and Basler, {Christopher F.}",
year = "2013",
month = "7",
day = "17",
doi = "10.1016/j.chom.2013.06.010",
language = "English (US)",
volume = "14",
pages = "74--84",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Mutual antagonism between the ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome

AU - Luthra, Priya

AU - Ramanan, Parameshwaran

AU - Mire, Chad

AU - Weisend, Carla

AU - Tsuda, Yoshimi

AU - Yen, Benjamin

AU - Liu, Gai

AU - Leung, Daisy W.

AU - Geisbert, Thomas

AU - Ebihara, Hideki

AU - Amarasinghe, Gaya K.

AU - Basler, Christopher F.

PY - 2013/7/17

Y1 - 2013/7/17

N2 - The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection.

AB - The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection.

UR - http://www.scopus.com/inward/record.url?scp=84880445500&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880445500&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2013.06.010

DO - 10.1016/j.chom.2013.06.010

M3 - Article

VL - 14

SP - 74

EP - 84

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 1

ER -