Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein

Krug, Robert M.; Yuan, Weiming; Noah, Diana L.; Latham, Anita Ghate

doi:10.1016/s0042-6822(03)00119-3

Cited by 238 publications

(225 citation statements)

References 80 publications

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“…NS1 also inhibits the activation of another cellular antiviral gene, protein kinase R (PKR). Activation of PKR is known to phosphorylate the ␣-subunit of the translation initiation factor eIF2 to inhibit protein synthesis and therefore virus replication (15). Our data present further evidence that NS1 antagonizes the host antiviral response by targeting and inhibiting RIG-I signaling to block IRF-3 activation.…”

Section: Rig-i-initiated Induction Of Type I Ifn Is Inhibited By Ns1 supporting

confidence: 60%

“…To further determine the interaction between RIG-I and NS1, constructs that expressed domains of RIG-I or NS1 and IFN-␤-CAT reporter plasmids were transfected with or without the full-length NS1 or RIG-I expression vectors into A549 cells ( Figure 5A NS1 of IAV is a multifunctional viral protein (15). Two cellular proteins that are required for the 3Ј-end processing of cellular pre-mRNAs, the 30-kD subunit of the cleavage and polyadenylation specificity factor (CPSF) and poly (A)-binding protein II (PABII), are bound and inactivated by IAV NS1, leading to decreased expression of the early type I IFN-independent antiviral genes (15).…”

Section: Rig-i-initiated Induction Of Type I Ifn Is Inhibited By Ns1 mentioning

confidence: 99%

“…Two cellular proteins that are required for the 3Ј-end processing of cellular pre-mRNAs, the 30-kD subunit of the cleavage and polyadenylation specificity factor (CPSF) and poly (A)-binding protein II (PABII), are bound and inactivated by IAV NS1, leading to decreased expression of the early type I IFN-independent antiviral genes (15). NS1 also inhibits the activation of another cellular antiviral gene, protein kinase R (PKR).…”

Section: Rig-i-initiated Induction Of Type I Ifn Is Inhibited By Ns1 mentioning

confidence: 99%

See 2 more Smart Citations

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

Guo

Chen

Zeng

et al. 2007

Am J Respir Cell Mol Biol

266

221

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Retinoic acid-inducible gene I (RIG-I) has recently been identified as one of the key intracellular sensors of virus infection. RIG-I binds to cytosolic double-stranded RNA and initiates a signaling cascade that leads to the activation of transcription factors required for expression of type I interferon (IFN-I). Previous evidence suggests that nonstructural protein 1 (NS1) encoded by influenza A virus (IAV) suppresses IFN-I secretion in virus-infected cells by an unknown mechanism. In the present study, we demonstrate that RIG-I is required

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Section: Rig-i-initiated Induction Of Type I Ifn Is Inhibited By Ns1 supporting

confidence: 60%

Section: Rig-i-initiated Induction Of Type I Ifn Is Inhibited By Ns1 mentioning

confidence: 99%

Section: Rig-i-initiated Induction Of Type I Ifn Is Inhibited By Ns1 mentioning

confidence: 99%

See 1 more Smart Citation

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

Guo

Chen

Zeng

et al. 2007

Am J Respir Cell Mol Biol

266

221

View full text Add to dashboard Cite

show abstract

“…The diverse observations may also be a result of differences in influenza virus subtypes and strains, as well as the host cell system being used in the experiments. Therefore, a detail characterization of the protein and the mechanisms involved in the induction of apoptosis is essential for understanding the pathogenesis of influenza viruses, particularly H5N1 (22).…”

Section: Discussionmentioning

confidence: 99%

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

Lam

Tang²,

Yeung³

et al. 2008

J Virol

107

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Avian H5N1 influenza virus causes a remarkably severe disease in humans, with an overall case fatality rate of greater than 50%. Human influenza A viruses induce apoptosis in infected cells, which can lead to organ dysfunction. To verify the role of H5N1-encoded NS1 in inducing apoptosis, the NS1 gene was cloned and expressed in human airway epithelial cells (NCI-H292 cells). The apoptotic events posttransfection were examined by a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end-labeling assay, flow cytometric measurement of propidium iodide, annexin V staining, and Western blot analyses with antibodies specific for proapoptotic and antiapoptotic proteins. We demonstrated that the expression of H5N1 NS1 protein in NCI-H292 cells was sufficient to induce apoptotic cell death. Western blot analyses also showed that there was prominent cleavage of poly(ADP-ribose) polymerase and activation of caspase-3, caspase-7, and caspase-8 during the NS1-induced apoptosis. The results of caspase inhibitor assays further confirmed the involvement of caspase-dependent pathways in the NS1-induced apoptosis. Interestingly, the ability of H5N1 NS1 protein to induce apoptosis was much enhanced in cells pretreated with Fas ligand (the time posttransfection required to reach >30% apoptosis was reduced from 24 to 6 h). Furthermore, 24 h posttransfection, an increase in Fas ligand mRNA expression of about 5.6-fold was detected in cells transfected with H5N1 NS1. In conclusion, we demonstrated that the NS1 protein encoded by avian influenza A virus H5N1 induced apoptosis in human lung epithelial cells, mainly via the caspase-dependent pathway, which encourages further investigation into the potential for the NS1 protein to be a novel therapeutic target.

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“…Although both products differ in characteristics, the s7ORF1 is nonstructural, primarily localized in the cytoplasm and unable to bind RNA while the s8ORF2 is structural, predominant localized in the nucleus and able to bind RNA, both can antagonize the interferon type I response [41,42]. In FluA segment 8 encodes the non-structural IFN-antagonist NS1 [43]. Sensitivity to the inhibitory actions of Mx GTPases is a characteristic property of all orthomyxoviruses [2].…”

Section: Interplay With Innate Immune Responsementioning

confidence: 99%

Comparative aspects of infectious salmon anemia virus, an orthomyxovirus of fish, to influenza viruses

2009

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Infectious salmon anaemia (ISA) is a viral disease that was fi rst recorded in 1984 in farmed Atlantic salmon. The infectious salmon anaemia virus (ISAV) is classifi ed as the type species of the genus Isavirus in the Orthomyxoviridae family and is evolutionary remote to the infl uenza viruses. The genome consists of eight negative single-stranded RNA segments, and it utilises the same mechanisms as infl uenza viruses to enter and exit cells. Although a common ancestor of ISAV and other genera of Orthomyxoviruses could be dated back several millions of years, there are still many similarities between ISAV and the infl uenza viruses regarding morphology, replication cycles and interactions with their respective hosts.

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Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein

Cited by 238 publications

References 80 publications

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

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

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

Comparative aspects of infectious salmon anemia virus, an orthomyxovirus of fish, to influenza viruses

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