Influenza Virus NS1 Protein Counteracts PKR-Mediated Inhibition of Replication
Open accessAbstract
The availability of an influenza virus NS1 gene knockout virus (delNS1 virus) allowed us to establish the significance of the biological relationship between the influenza virus NS1 protein and double-stranded-RNA-activated protein kinase (PKR) in the life cycle and pathogenicity of influenza virus. Our results show that the lack of functional PKR permits the delNS1 virus to replicate in otherwise nonpermissive hosts, suggesting that the major function of the influenza virus NS1 protein is to counteract or prevent the PKR-mediated antiviral response.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The influenza virus NS1 protein inhibits PKR activation, resulting in increased viral replication in the lung.
“The influenza virus NS1 protein, for example, inhibits PKR activation, resulting in increased viral replication in the lung (20).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [20]
Cites
Targeted Disruption of the Mouse Stat1 Gene Results in Compromised Innate Immunity to Viral Disease
Durbin, J. E., Hackenmiller, R., Simon, M. C., & Levy, D. E. (1996) · Cell · doi:10.1016/s0092-8674(00)81289-1 · Cited by 1,522 · see citing works
MEURS, E. F., Chong, K. L., GALABRU, J., Thomas, N. S. B., Kerr, I. M., Williams, B. R. G., & Hovanessian, A. G. (1990) · Cell · doi:10.1016/0092-8674(90)90374-n · Cited by 1,017 · see citing works
Influenza A Virus Lacking the NS1 Gene Replicates in Interferon-Deficient Systems
García‐Sastre, A., Egorov, A., Matassov, D., Brandt, S., Levy, D. E., Durbin, J. E., Palese, P., & Muster, T. (1998) · Virology · doi:10.1006/viro.1998.9508 · Cited by 1,000 · see citing works
Self-citationPKR; a sentinel kinase for cellular stress
Williams, B. R. (1999) · Oncogene · doi:10.1038/sj.onc.1203127 · Cited by 820 · see citing works
Reovirus Therapy of Tumors with Activated Ras Pathway
Coffey, M. C., Strong, J. E., Forsyth, P. A., & Lee, P. W. K. (1998) · Science · doi:10.1126/science.282.5392.1332 · Cited by 750 · see citing works
Deficient signaling in mice devoid of double‐stranded RNA‐dependent protein kinase.
Yang, Y. L., Reis, L. F. L., Pavlovic, J., Aguzzi, A., Schäfer, R., Kumar, A., Williams, B. R. G., Aguet, M., & Weissmann, C. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00300.x · Cited by 632 · see citing works
Samuel, C. E. (1991) · Virology · doi:10.1016/0042-6822(91)90112-o · Cited by 608 · see citing works
The Double-Stranded RNA-Dependent Protein Kinase PKR: Structure and Function
Clemens, M. J., & Elia, A. (1997) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.1997.17.503 · Cited by 605 · see citing works
The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus
Strong, J. E., Coffey, M. C., Tang, D., Sabinin, P., & Lee, P. W. K. (1998) · The EMBO Journal · doi:10.1093/emboj/17.12.3351 · Cited by 552 · see citing works
Gale, M., & Katze, M. G. (1998) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(97)00165-4 · Cited by 388 · see citing works
LU, Y., Wambach, M., Katze, M. G., & Krug, R. M. (1995) · Virology · doi:10.1006/viro.1995.9937 · Cited by 387 · see citing works
Interferon Action: RNA Cleavage Pattern of a (2′-5′)Oligoadenylate—Dependent Endonuclease
Floyd-Smith, G., Slattery, E., & Lengyel, P. (1981) · Science · doi:10.1126/science.6165080 · Cited by 362 · see citing works
Kumar, A., Yang, Y., Flati, V., Der, S., Kadereit, S., Deb, A., Haque, J., Reis, L. F. L., Weissmann, C., & Williams, B. R. G. (1997) · The EMBO Journal · doi:10.1093/emboj/16.2.406 · Cited by 350 · see citing works
Influenza Virus-Susceptible Mice Carry Mx Genes with a Large Deletion or a Nonsense Mutation
Staeheli, P., Grob, R., Meier, E., Sutcliffe, J. G., & Haller, O. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.10.4518-4523.1988 · Cited by 294 · see citing works
Influenza virus NS1 protein inhibits pre‐mRNA splicing and blocks mRNA nucleocytoplasmic transport.
Fortes, P., Beloso, A., & Ortı́n, J. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06310.x · Cited by 278 · see citing works
Hoess, A., Watson, S., Siber, G. R., & Liddington, R. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06008.x · Cited by 255 · see citing works
Interferon Action in Triply Deficient Mice Reveals the Existence of Alternative Antiviral Pathways
Zhou, A., Paranjape, J. M., Der, S. D., Williams, B. R. G., & Silverman, R. H. (1999) · Virology · doi:10.1006/viro.1999.9738 · Cited by 244 · see citing works
Qiu, Y., & Krug, R. M. (1994) · Journal of Virology · doi:10.1128/jvi.68.4.2425-2432.1994 · Cited by 237 · see citing works
Abraham, N. B., Stojdl, D. F., Duncan, P. I., Méthot, N., Ishii, T. M., Dubé, M., Vanderhyden, B. C., Atkins, H. L., Gray, D. A., McBurney, M. W., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.9.5953 · Cited by 231 · see citing works
Egorov, A., Brandt, S., Sereinig, S., et al. (1998) · Journal of Virology · doi:10.1128/jvi.72.8.6437-6441.1998 · Cited by 220 · see citing works
The Double Stranded RNA-Activated Protein Kinase Induced by Interferon: dsRNA-PK
Hovanessian, A. G. (1989) · Journal of Interferon Research · doi:10.1089/jir.1989.9.641 · Cited by 201 · see citing works
Tumor-suppressor genes: news about the interferon connection.
Lengyel, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.13.5893 · Cited by 199 · see citing works
The influenza virus NS1 protein: a novel inhibitor of pre-mRNA splicing.Preprint
Lu, Y., Qian, X. Y., & Krug, R. M. (1994) · Genes & Development · doi:10.1101/gad.8.15.1817 · Cited by 182 · see citing works
Hatada, E., Saito, S., & Fukuda, R. (1999) · Journal of Virology · doi:10.1128/jvi.73.3.2425-2433.1999 · Cited by 177 · see citing works
Ronni, T., Sareneva, T., Pirhonen, J., et al. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.6.2764 · Cited by 166 · see citing works
Ronni, T., Matikainen, S., Sareneva, T., Melén, K., Pirhonen, J., Keskinen, P., & Julkunen, I. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.5.2363 · Cited by 155 · see citing works
Qiu, Y., Nemeroff, M. E., & Krug, R. M. (1995) · PubMed · Cited by 152 · see citing works
Tan, S., & Katze, M. G. (1998) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.1998.18.757 · Cited by 141 · see citing works
Melville, M. W., Tan, S., Wambach, M., Song, J., Morimoto, R. I., & Katze, M. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.6.3797 · Cited by 129 · see citing works
2-Aminopurine Inhibits the Double-Stranded RNA-Dependent Protein Kinase Both In Vitro and In Vivo
HU, Y., & Conway, T. W. (1993) · Journal of Interferon Research · doi:10.1089/jir.1993.13.323 · Cited by 115 · see citing works
Mundschau, L. J., & Faller, D. V. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50061-2 · Cited by 109 · see citing works
Katze, M. G., Tomita, J., Black, T. L., et al. (1988) · Journal of Virology · doi:10.1128/jvi.62.10.3710-3717.1988 · Cited by 108 · see citing works
The molecular chaperone hsp40 regulates the activity of P58 IPK , the cellular inhibitor of PKR
Melville, M. W., Hansen, W. J., Freeman, B., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.1.97 · Cited by 104 · see citing works
Interaction of influenza virus NS1 protein and the human homologue of Staufen in vivo and in vitro
Falcón, A. M., Fortes, P., Marión, R. M., Beloso, A., & Ortı́n, J. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.11.2241 · Cited by 95 · see citing works
Gale, M., Blakely, C. M., Hopkins, D. A., Melville, M. W., Wambach, M., Romano, P. R., & Katze, M. G. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.2.859 · Cited by 85 · see citing works
Marión, R. M., Aragón, T., Beloso, A., et al. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.21.4271 · Cited by 66 · see citing works
Jansen, B., Schlagbauer‐Wadl, H., Eichler, H. G., Wolff, K., van Elsas, A., Schrier, P. I., & Pehamberger, H. (1997) · PubMed · Cited by 64 · see citing works
Self-citationCleavage of Oligoribonucleotides by the 2′,5′-Oligoadenylate- dependent Ribonuclease L
Carroll, S. S., Chen, E., Viscount, T., Geib, J., Sardana, M. K., Gehman, J. D., & Kuo, L. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.9.4988 · Cited by 61 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Antiviral Actions of Interferons
Samuel, C. E. (2001) · Clinical Microbiology Reviews · doi:10.1128/cmr.14.4.778-809.2001 · Cited by 2,743 · see citing works
Interferon-inducible antiviral effectors
Sadler, A. J., & Williams, B. R. G. (2008) · Nature Reviews Immunology · doi:10.1038/nri2314 · Cited by 2,160 · see citing works
Viruses and interferon: a fight for supremacy
Katze, M. G., He, Y., & Gale, M. (2002) · Nature Reviews Immunology · doi:10.1038/nri888 · Cited by 1,419 · see citing works
ISG15 in antiviral immunity and beyond
Perng, Y.-C., & Lenschow, D. J. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0020-5 · Cited by 855 · see citing works
The airway epithelium: soldier in the fight against respiratory viruses
Vareille, M., Kieninger, E., Edwards, M. R., & Regamey, N. (2011) · Clinical Microbiology Reviews · doi:10.1128/cmr.00014-10 · Cited by 655 · see citing works
The dsRNA protein kinase PKR: Virus and cell control
García, M. A., Meurs, E. F., & Esteban, M. (2007) · Biochimie · doi:10.1016/j.biochi.2007.03.001 · Cited by 644 · see citing works
The virus battles: IFN induction of the antiviral state and mechanisms of viral evasion
Levy, D. (2001) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(00)00027-7 · Cited by 428 · see citing works
Bradley, K. C., Finsterbusch, K., Schnepf, D., Crotta, S., Llorian, M., Davidson, S., Fuchs, S. Y., Staeheli, P., & Wack, A. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.105 · Cited by 313 · see citing works
Host defense function of the airway epithelium in health and disease: clinical background
Message, S. D., & Johnston, S. L. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0703315 · Cited by 159 · see citing works
- Authors
- Bergmann, M., Garcia-Sastre, A., Carnero, E., Pehamberger, H., Wolff, K., Palese, P., & Muster, T.
- Affiliations
- <!--label omitted: 1-->Department of Surgery1and
- <!--label omitted: 2-->Department of Microbiology, Mount Sinai Medical Center, New York, New York 100292
- Icahn School of Medicine at Mount Sinai (US)
- University of Vienna (AT)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2000-07
- Volume
- 74
- Issue
- 13
- Pages
- 6203-6206
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC112122
- OpenAlex
- W2151778974
- Cited by
- 362
- References
- 38
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 13 · 2020: 8 · 2019: 13 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 14 · 2013: 10 · 2012: 18
- FWCI
- 14.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- PKR, double-stranded RNA-dependent protein kinase, antiviral response, viral replication, host-pathogen interaction, viral pathogenicity, interferon-stimulated genes
- MeSH terms
- Animals, Disease Models, Animal, DNA-Binding Proteins, Humans, Influenza, Human, Interferons, Lung, Mice, Inbred C57BL, Influenza A virus, Virus Replication, Trans-Activators, Viral Nonstructural Proteins, Mice, Knockout, eIF-2 Kinase, STAT1 Transcription Factor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review