Epstein-Barr virus deubiquitinase downregulates TRAF6-mediated NF-κB signaling during productive replication

Shinichi Saito, Takayuki Murata, Teru Kanda, Hiroki Isomura, Yohei Narita, Atsuko Sugimoto, Daisuke Kawashima, Tatsuya Tsurumi

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV), a human oncogenic herpesvirus that establishes a lifelong latent infection in the host, occasionally enters lytic infection to produce progeny viruses. The EBV oncogene latent membrane protein 1 (LMP1), which is expressed in both latent and lytic infection, constitutively activates the canonical NF-κB (p65) pathway. Such LMP1-mediated NF-κB activation is necessary for proliferation of latently infected cells and inhibition of viral lytic cycle progression. Actually, canonical NF-κB target gene expression was suppressed upon the onset of lytic infection. TRAF6, which is activated by conjugation of polyubiquitin chains, associates with LMP1 to mediate NF-κB signal transduction. We have found that EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-κB signaling during lytic infection. HEK293 cells with BPLF1-deficient recombinant EBV exhibited poor viral DNA replication compared with the wild type. Furthermore, exogenous expression of BPLF1 or p65 knockdown in cells restored DNA replication of BPLF1-deficient viruses, indicating that EBV BPLF1 deubiquitinates TRAF6 to inhibit NF-κB signal transduction, leading to promotion of viral lytic DNA replication

Original languageEnglish
Pages (from-to)4060-4070
Number of pages11
JournalJournal of Virology
Volume87
Issue number7
DOIs
Publication statusPublished - 01-04-2013

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TNF Receptor-Associated Factor 6
Human herpesvirus 4
Human Herpesvirus 4
Down-Regulation
DNA replication
DNA Replication
membrane proteins
Infection
infection
Viral DNA
signal transduction
Signal Transduction
Membrane Proteins
Polyubiquitin
Viruses
viruses
HEK293 Cells
Herpesviridae
oncogenes
cells

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Saito, Shinichi ; Murata, Takayuki ; Kanda, Teru ; Isomura, Hiroki ; Narita, Yohei ; Sugimoto, Atsuko ; Kawashima, Daisuke ; Tsurumi, Tatsuya. / Epstein-Barr virus deubiquitinase downregulates TRAF6-mediated NF-κB signaling during productive replication. In: Journal of Virology. 2013 ; Vol. 87, No. 7. pp. 4060-4070.
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Saito, S, Murata, T, Kanda, T, Isomura, H, Narita, Y, Sugimoto, A, Kawashima, D & Tsurumi, T 2013, 'Epstein-Barr virus deubiquitinase downregulates TRAF6-mediated NF-κB signaling during productive replication', Journal of Virology, vol. 87, no. 7, pp. 4060-4070. https://doi.org/10.1128/JVI.02020-12

Epstein-Barr virus deubiquitinase downregulates TRAF6-mediated NF-κB signaling during productive replication. / Saito, Shinichi; Murata, Takayuki; Kanda, Teru; Isomura, Hiroki; Narita, Yohei; Sugimoto, Atsuko; Kawashima, Daisuke; Tsurumi, Tatsuya.

In: Journal of Virology, Vol. 87, No. 7, 01.04.2013, p. 4060-4070.

Research output: Contribution to journalArticle

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