NS1 Protein of Influenza A Virus Inhibits the Function of Intracytoplasmic Pathogen Sensor, RIG-I

Guo, Zhu; Chen, Limei; Zeng, Hui; Gómez, Jorge; Plowden, Julie; Fujita, Takashi; Katz, Jacqueline M.; Donis, Ruben O.; Sambhara, Suryaprakash

doi:10.1165/rcmb.2006-0283rc

Cited by 267 publications

(239 citation statements)

References 15 publications

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…For example, the NS1 protein of the influenza A virus inhibits the function of RIG-I, thus downregulating type I IFN expression. 18,19 The V proteins of paramyxoviruses interact with MDA-5 to block its activity, which leads to a reduction in IFN-b promoter activation. 20 The cysteine protease NS3/4A of hepatitis C virus cleaves VISA and the TLR3 adapter protein TRIF, thereby blocking RIG-I-and TLR3-mediated induction of the type I IFNs.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

“…For example, NS1 blocks 29-59-oligoadenylate synthetase-mediated activation of RNase L (Min & Krug, 2006) and limits the induction of IFN-b (Wang et al, 2000;Ludwig et al, 2002). Furthermore, NS1 binds to and inhibits the cytoplasmic dsRNA sensor retinoic acidinducible gene product I (Guo et al, 2007;Mibayashi et al, 2007) and blocks protein kinase R-mediated inhibition of protein synthesis (Bergmann et al, 2000;Min et al, 2007). In addition to its IFN antagonistic activities, NS1 has recently been shown to actively suppress RNA silencing in plant, insect and mammalian cells (Bucher et al, 2004;Delgadillo et al, 2004;Li et al, 2004;Haasnoot et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Differential RNA silencing suppression activity of NS1 proteins from different influenza A virus strains

Vries

Haasnoot

Fouchier³

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

The NS1 gene of influenza A virus encodes a multi-functional protein that plays an important role in counteracting cellular antiviral mechanisms such as the interferon (IFN), protein kinase R and retinoic acid-inducible gene product I pathways. In addition, NS1 has recently been shown to have RNA interference (RNAi) or RNA silencing suppression (RSS) activity. This study analysed the IFN antagonistic activity of NS1 and the RSS activity for several influenza subtypes: H1N1, H3N2, H5N1 and H7N7. It was shown that the various NS1 proteins were capable of inhibiting the activation of an IFN-responsive promoter. However, differential RSS activity was measured among the NS1 variants. The NS1 protein of strain A/WSN/33 (H1N1) was most potent in suppressing short hairpin RNA-mediated gene silencing. In contrast, NS1 proteins of the highly pathogenic H5N1 strains A/VN/1194/04 and A/HK/156/97 were most potent in complementing the RSS function of the human immunodeficiency virus type 1 Tat protein. These results show that the ability of NS1 to suppress RNAi varies among influenza strains and is likely to contribute to differences in viral replication capacity and pathogenicity.

show abstract

“…However, the majority of previous work has focused on the ability of NS1 to circumvent the host cell antiviral responses. This is achieved in a number of ways, including blocking 2Ј-5Ј-oligoadenylate synthetase (2Ј-5Ј-OAS) activation of RNaseL (18), limiting the induction of IFN-␤ by preventing the activation of transcription factors (19)(20)(21), interaction with the cellular protein retinoic acid-inducible gene product I (RIG-I) (22)(23)(24), blocking host cell mRNA polyadenylation (25,26), and blocking the PKR-mediated inhibition of protein synthesis (13,27). It has also been shown that NS1 prevents the maturation of human primary dendritic cells, thereby limiting host T cell activation (28).…”

mentioning

confidence: 99%

A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity

Jackson

Hossain

Hickman

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

367

306

View full text Add to dashboard Cite

The virulence of influenza virus is a multigenic trait. One determinant of virulence is the multifunctional NS1 protein that functions in several ways to defeat the cellular innate immune response. Recent large-scale genome sequence analysis of avian influenza virus isolates indicated that four C-terminal residues of the NS1 protein is a PDZ ligand domain of the X-S/T-X-V type and it was speculated that it may represent a virulence determinant. To test this hypothesis, by using mice as a model system, the four Cterminal amino acid residues of a number of influenza virus strains were engineered into the

show abstract

NS1 Protein of Influenza A Virus Inhibits the Function of Intracytoplasmic Pathogen Sensor, RIG-I

Cited by 267 publications

References 15 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

Differential RNA silencing suppression activity of NS1 proteins from different influenza A virus strains

A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity

Contact Info

Product

Resources

About