GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS

Zihong Chen, Yann Benureau, Rene Rijnbrand, Jianzhong Yi, Ting Wang, Lucile Warter, Robert E. Lanford, Steven A. Weinman, Stanley M. Lemon, Annette Martin, Kui Li

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Understanding the mechanisms of hepatitis C virus (HCV) pathogenesis and persistence has been hampered by the lack of small, convenient animal models. GB virus B (GBV-B) is phylogenetically the closest related virus to HCV. It causes generally acute and occasionally chronic hepatitis in small primates and is used as a surrogate model for HCV. It is not known, however, whether GBV-B has evolved strategies to circumvent host innate defenses similar to those of HCV, a property that may contribute to HCV persistence in vivo. We show here in cultured tamarin hepatocytes that GBV-B NS3/4A protease, but not a related catalytically inactive mutant, effectively blocks innate intracellular antiviral responses signaled through the RNA helicase, retinoic acid-inducible gene I (RIG-I), an essential sensor molecule that initiates host defenses against many RNA viruses, including HCV. GBV-B NS3/4A protease specifically cleaves mitochondrial antiviral signaling protein (MAVS; also known as IPS-1/Cardif/VISA) and dislodges it from mitochondria, thereby disrupting its function as a RIG-I adaptor and blocking downstream activation of both interferon regulatory factor 3 and nuclear factor kappa B. MAVS cleavage and abrogation of virus-induced interferon responses were also observed in Huh7 cells supporting autonomous replication of subgenomic GBV-B RNAs. Our data indicate that, as in the case of HCV, GBV-B has evolved to utilize its major protease to disrupt MG-1 signaling and impede innate antiviral defenses. These data provide further support for the use of GBV-B infection in small primates as an accurate surrogate model for deciphering virus-host interactions in hepacivirus pathogenesis.

Original languageEnglish (US)
Pages (from-to)964-976
Number of pages13
JournalJournal of Virology
Volume81
Issue number2
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Fingerprint

Hepatitis GB virus B
GB virus B
Hepatitis C virus
retinoic acid
Tretinoin
Hepacivirus
Genes
Proteins
genes
proteins
proteinases
Antiviral Agents
Peptide Hydrolases
viruses
Viruses
Primates
pathogenesis
RNA helicases
chronic hepatitis
Interferon Regulatory Factor-3

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS. / Chen, Zihong; Benureau, Yann; Rijnbrand, Rene; Yi, Jianzhong; Wang, Ting; Warter, Lucile; Lanford, Robert E.; Weinman, Steven A.; Lemon, Stanley M.; Martin, Annette; Li, Kui.

In: Journal of Virology, Vol. 81, No. 2, 01.01.2007, p. 964-976.

Research output: Contribution to journalArticle

Chen, Z, Benureau, Y, Rijnbrand, R, Yi, J, Wang, T, Warter, L, Lanford, RE, Weinman, SA, Lemon, SM, Martin, A & Li, K 2007, 'GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS', Journal of Virology, vol. 81, no. 2, pp. 964-976. https://doi.org/10.1128/JVI.02076-06
Chen, Zihong ; Benureau, Yann ; Rijnbrand, Rene ; Yi, Jianzhong ; Wang, Ting ; Warter, Lucile ; Lanford, Robert E. ; Weinman, Steven A. ; Lemon, Stanley M. ; Martin, Annette ; Li, Kui. / GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS. In: Journal of Virology. 2007 ; Vol. 81, No. 2. pp. 964-976.
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AU - Lanford, Robert E.

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