VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling

Xu, Liang‐Guo; Wang, Yan-Yi; Han, Ke-Jun; Li, Lianyun; Zhai, Zhonghe; Shu, Hong‐Bing

doi:10.1016/j.molcel.2005.08.014

Cited by 1,685 publications

(1,478 citation statements)

References 44 publications

Supporting

Mentioning

1,409

Contrasting

Unclassified

Order By: Relevance

“…Tumor-necrosis factor-a and IL-1b (R&D Systems, Minneapolis, MN, USA), mouse monoclonal antibodies against Flag and HA (Sigma, St Louis, MO, USA) and rabbit polyclonal antibodies against IRF3 and MDA5 (Santa Cruz Biotechnology, Santa Cruz, CA, USA) were purchased from the indicated manufacturers; SeV and VSV were previously described. 7,36,37 Plasmids A plasmid carrying a greater-than-unit-length (129%) HBV genome (payw1.2; subtype ayw) and the same plasmid with a stop codon replacing the coding sequence for amino acid 7 of HBx (payw*7) were previously described. 34,35 The vector pEGFP-C1 was a gift provided by Yan Wu.…”

Section: Methodsmentioning

confidence: 99%

“…Luciferase reporter plasmids for NF-kB, ISRE and the IFN-b promoters, as well as mammalian expression plasmids for HA-or Flag-tagged RIG-I, RIG-I-N, MDA5, MDA5-N, MDA5-C, VISA, TBK1, MITA and IRF3, were previously described. 7,11,36,37 Expression plasmids for human HA-, Flag-or GFP-tagged HBx and RFP-tagged RIG-I, MDA5 and VISA were constructed by standard molecular biology techniques.…”

Section: Methodsmentioning

confidence: 99%

“…The helicase domains of RIG-I and MDA5 serve as intracellular viral RNA receptors, whereas the CARD modules are responsible for transmitting signals to the downstream CARD-containing adapter protein VISA (also known as MAVS, IPS-1 and Cardif). [7][8][9][10] The C-terminus of VISA contains a transmembrane domain that anchors VISA to the outer membrane of the mitochondria, implying an important role of mitochondria in innate antiviral immunity. 8 On the outer membrane of the mitochondria, VISA acts as a central adapter for assembling a virus-induced complex that activates distinct signaling pathways leading to IFN-regulatory factor-3 (IRF3) and nuclear factorkappaB (NF-kB) activation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-β induction by disrupting the VISA-associated complex

Wang

Mao

et al. 2010

Cell Mol Immunol

View full text Add to dashboard Cite

Viral RNAs produced during viral infection are recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). A central adapter protein downstream of RIG-I and MDA5 is the mitochondrial membrane protein virus-induced signaling adaptor (VISA), which mediates the induction of type I interferons (IFNs) through the activation of transcription factors such as nuclear factor-kappaB (NF-kB) and IFN-regulatory factor-3 (IRF3). Here we found that hepatitis B virus (HBV)-encoded X protein (HBx) acts as an inhibitor of virus-triggered IRF3 activation and IFN-b induction. Reporter and plaque assays indicate that HBx inhibits signaling by components upstream but not downstream of VISA. Immunoprecipitation experiments indicate that HBx interacts with VISA and disrupts the association of VISA with its upstream and downstream components. These findings suggest that HBx acts as a suppressor of virus-triggered induction of type I IFNs, which explains the observation that HBV causes transient and chronic infection in hepatocytes but fails to activate the pattern recognition receptor-mediated IFN induction pathways.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-β induction by disrupting the VISA-associated complex

Wang

Mao

et al. 2010

Cell Mol Immunol

View full text Add to dashboard Cite

show abstract

“…The link between these two proteins and NF-kB remains somewhat unclear ( Figure 5c); however overexpression of the N-terminal CARD domain alone is sufficient to induce signaling. Recently, a CARD-containing protein, variably named CARDIF, IPS1, MAVS and VISA, has been implicated downstream of RIG-I; however, the link between this protein and IKKb is unclear Meylan et al, 2005;Seth et al, 2005;Xu et al, 2005). It appears, however, that there are similarities to TRIF mediated signaling, in that RIG-I activation of NF-kB requires FADD and RIP-1 (Balachandran et al, 2004;Yoneyama et al, 2005).…”

Section: Retinoic Acid Inducible Gene I and Melanoma Differentiation-mentioning

confidence: 99%

NF-κB and the immune response

2006

View full text Add to dashboard Cite

“…Retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytoplasmic RNA helicases [1][2][3], which signal the presence of viral RNA through the adaptor, IFN-b promoter stimulator-1 (IPS-1) (also known as mitochondrial antiviral signaling protein/caspase recruitment domain (CARD) adaptor inducing IFN-b (Cardif)/virus-induced signaling adaptor) to produce IFN-b [4][5][6][7]. IPS-1 localizes on the outer membrane of the mitochondria via its C-terminus [6].…”

Section: Introductionmentioning

confidence: 99%

DEAD/H BOX 3 (DDX3) helicase binds the RIG‐I adaptor IPS‐1 to up‐regulate IFN‐β‐inducing potential

et al. 2010

View full text Add to dashboard Cite

Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLR) are members of the DEAD box helicases, and recognize viral RNA in the cytoplasm, leading to IFN-b induction through the adaptor IFN-b promoter stimulator-1 (IPS-1) (also known as Cardif, mitochondrial antiviral signaling protein or virus-induced signaling adaptor). Since uninfected cells usually harbor a trace of RIG-I, other RNA-binding proteins may participate in assembling viral RNA into the IPS-1 pathway during the initial response to infection. We searched for proteins coupling with human IPS-1 by yeast two-hybrid and identified another DEAD (Asp-Glu-AlaAsp) box helicase, DDX3 (DEAD/H BOX 3). DDX3 can bind viral RNA to join it in the IPS-1 complex. Unlike RIG-I, DDX3 was constitutively expressed in cells, and some fraction of DDX3 is colocalized with IPS-1 around mitochondria. The 622-662 a.a DDX3 C-terminal region (DDX3-C) directly bound to the IPS-1 CARD-like domain, and the whole DDX3 protein also associated with RLR. By reporter assay, DDX3 helped IPS-1 up-regulate IFN-b promoter activation and knockdown of DDX3 by siRNA resulted in reduced IFN-b induction. This activity was conserved on the DDX3-C fragment. DDX3 only marginally enhanced IFN-b promoter activation induced by transfected TANK-binding kinase 1 (TBK1) or I-kappa-B kinase-e (IKKe). Forced expression of DDX3 augmented virus-mediated IFN-b induction and host cell protection against virus infection. Hence, DDX3 is an antiviral IPS-1 enhancer. IntroductionRetinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytoplasmic RNA helicases [1][2][3], which signal the presence of viral RNA through the adaptor, IFN-b promoter stimulator-1 (IPS-1) (also known as mitochondrial antiviral signaling protein/caspase recruitment domain (CARD) adaptor inducing IFN-b (Cardif)/virus-induced signaling adaptor) to produce . IPS-1 localizes on the outer membrane of the mitochondria via its C-terminus [6]. Its Nterminus consists of a CARD domain, which interacts with the CARD domains of RIG-I and MDA5. Viral RNA resulting from penetration or replication are believed to assemble in the CARDinteracting helicase complex to activate the cytoplasmic IFNinducing pathway. Although non-infected cells usually express minimal amounts of RIG-I/MDA5, the final output of type I IFN is efficiently induced at an early stage of infection to protect host cells from viral spreading.Once IPS-1 is activated, the kinase complex consisting of TANK-homologous proteins and virus-activated kinases induce nuclear translocation of IFN regulatory factor-3 (IRF-3) to activate the IFN promoter [8]. NAK-associated protein 1, TANKbinding kinase 1 (TBK1) and I-kappa-B kinase-e (IKKe) are components of the kinase complex that phosphorylates IRF-3 to induce type I IFN [9,10]. RIG-I recognizes products of various RNA viruses, while MDA5 recognizes products of picornaviruses 940Frontline [1,11]. RIG-I and MDA5 share the helicase domain, which is classified into the DEAD (Asp-Glu-Ala-Asp) box helicase...

show abstract

VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling

Cited by 1,685 publications

References 44 publications

Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-β induction by disrupting the VISA-associated complex

Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-β induction by disrupting the VISA-associated complex

NF-κB and the immune response

DEAD/H BOX 3 (DDX3) helicase binds the RIG‐I adaptor IPS‐1 to up‐regulate IFN‐β‐inducing potential

Contact Info

Product

Resources

About