The DOI matches its Crossref record; 47 of the 49 references it cites were found in a registry or an index.
Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection
Open accessAbstract
Periodic outbreaks of highly pathogenic avian H5N1 influenza viruses and the current H1N1 pandemic highlight the need for a more detailed understanding of influenza virus pathogenesis. To investigate the host transcriptional response induced by pathogenic influenza viruses, we used a functional-genomics approach to compare gene expression profiles in lungs from 129S6/SvEv mice infected with either the fully reconstructed H1N1 1918 pandemic virus (1918) or the highly pathogenic avian H5N1 virus Vietnam/1203/04 (VN/1203). Although the viruses reached similar titers in the lung and caused lethal infections, the mean time of death was 6 days for VN/1203-infected animals and 9 days for mice infected with the 1918 virus. VN/1203-infected animals also exhibited an earlier and more potent inflammatory response. This response included induction of genes encoding components of the inflammasome. VN/1203 was also able to disseminate to multiple organs, including the brain, which correlated with changes in the expression of genes associated with hematological functions and lipoxin biogenesis and signaling. Both viruses elicited expression of type I interferon (IFN)-regulated genes in wild-type mice and to a lesser extent in mice lacking the type I IFN receptor, suggesting alternative or redundant pathways for IFN signaling. Our findings suggest that VN/1203 is more pathogenic in mice as a consequence of several factors, including the early and sustained induction of the inflammatory response, the additive or synergistic effects of upregulated components of the immune response, and inhibition of lipoxin-mediated anti-inflammatory responses, which correlated with the ability of VN/1203 to disseminate to extrapulmonary organs.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“Cytokine signaling pathway redundancy is also observed with respect to type I IFN signaling, as there is strong upregulation of IFN-stimulated gene expression in IFN-␣/R KO mice infected with the 1918 virus (27).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [27]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,515
A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS
Reed, L., & Muench, H. (1938) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a118408 · Cited by 17,629
A simple method of estimating 50 per cent end points
Muench, H. (1938) · Medical Entomology and Zoology · Cited by 8,376
Origin and physiological roles of inflammation
Medzhitov, R. (2008) · Nature · doi:10.1038/nature07201 · Cited by 6,618
Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903810 · Cited by 3,063
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932
Functional Role of Type I and Type II Interferons in Antiviral Defense
Müller, U., Steinhoff, U., Reis, L. F. L., Hemmi, S., Pavlovic, J., Zinkernagel, R. M., & Aguet, M. (1994) · Science · doi:10.1126/science.8009221 · Cited by 2,453
Updating the accounts: global mortality of the 1918–1920 "Spanish" influenza pandemic.
Johnson, N. P. A. S., & Mueller, J. (2002) · Bulletin of the History of Medicine · doi:10.1353/bhm.2002.0022 · Cited by 1,980
Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings
Fraser, C., Donnelly, C. A., Cauchemez, S., Hanage, W. P., Kerkhove, M. D. V., Hollingsworth, T. D., Griffin, J. T., Baggaley, R. F., Jenkins, H. E., Lyons, E., et al. (2009) · Science · doi:10.1126/science.1176062 · Cited by 1,915
Emergence and pandemic potential of swine-origin H1N1 influenza virus
Neumann, G., Noda, T., & Kawaoka, Y. (2009) · Nature · doi:10.1038/nature08157 · Cited by 1,590
Biosafety in microbiological and biomedical laboratories
Richmond, J. Y., & McKinney, R. W. (1999) · U.S. G.P.O. , For sale by the Supt. of Docs., U.S. G.P.O. eBooks · Cited by 1,494
Characterization of the reconstructed 1918 Spanish influenza pandemic virus
Tumpey, T. M., Basler, C. F., Aguilar, P. V., Zeng, H., Solórzano, A., Swayne, D. E., Cox, N. J., Katz, J. M., Taubenberger, J. K., Palese, P., et al. (2005) · Science · doi:10.1126/science.1119392 · Cited by 1,327
Self-citationAllen, I. C., Scull, M. A., Moore, C. B., Holl, E. K., McElvania-TeKippe, E., Taxman, D. J., Guthrie, E. H., Pickles, R. J., & Ting, J. P.-Y. (2009) · Immunity · doi:10.1016/j.immuni.2009.02.005 · Cited by 1,113
Yuen, K., Chan, P., Peiris, M. J. S., Tsang, D., Que, T., Shortridge, K. F., Cheung, P., To, W., Ho, E., Sung, R. Y. T., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(98)01182-9 · Cited by 1,054
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
Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus.
Kobasa, D., Jones, S. M., Shinya, K., Kash, J. C., Copps, J., Ebihara, H., Hatta, Y., Hyun Kim, J., Halfmann, P., Hatta, M., et al. (2007) · Nature · doi:10.1038/nature05495 · Cited by 934
Self-citationRe-emergence of fatal human influenza A subtype H5N1 disease
Peiris, J., Yu, W., Leung, C., Cheung, C., Ng, W., Nicholls, J., Ng, T., Chan, K., Lai, S., Lim, W., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15595-5 · Cited by 812
Thomas, P. G., Dash, P., Aldridge, J. R., Ellebedy, A. H., Reynolds, C., Funk, A. J., Martin, W. J., Lamkanfi, M., Webby, R. J., Boyd, K. L., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.02.006 · Cited by 769
Inflammasome recognition of influenza virus is essential for adaptive immune responses
Ichinohe, T., Lee, H. K., Ogura, Y., Flavell, R. A., & Iwasaki, A. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20081667 · Cited by 701
A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission
Tumpey, T. M., Maines, T. R., Hoeven, N. V., Glaser, L. J., Solórzano, A., Pappas, C., Cox, N. J., Swayne, D. E., Palese, P., Katz, J. M., et al. (2007) · Science · doi:10.1126/science.1136212 · Cited by 580
Self-citationGenomic analysis of increased host immune and cell death responses induced by 1918 influenza virus
Kash, J. C., Tumpey, T. M., Proll, S. C., Carter, V., Perwitasari, O., Thomas, M. J., Basler, C. F., Palese, P., Taubenberger, J. K., García-Sastre, A., et al. (2006) · Nature · doi:10.1038/nature05181 · Cited by 551
Self-citationMaines, T. R., Lu, X. H., Erb, S. M., Edwards, L. E., Guarner, J., Greer, P. W., Nguyen, D. C., Szretter, K. J., Chen, L., Thawatsupha, P., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.18.11788-11800.2005 · Cited by 453
Self-citationAn Important Role for Type III Interferon (IFN-λ/IL-28) in TLR-Induced Antiviral Activity
Ank, N., Iversen, M. B., Bartholdy, C., Staeheli, P., Hartmann, R., Jensen, U. B., Dagnæs‐Hansen, F., Thomsen, A. R., Chen, Z. J., Haugen, H. S., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2474 · Cited by 431
Geisbert, T. W., Young, H. A., Jahrling, P. B., Davis, K. J., Kagan, E., & Hensley, L. E. (2003) · The Journal of Infectious Diseases · doi:10.1086/379724 · Cited by 373
Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors
van den Broek, M. F., Müller, U., Huang, S., Aguet, M., & Zinkernagel, R. M. (1995) · Journal of Virology · doi:10.1128/jvi.69.8.4792-4796.1995 · Cited by 362
Baskin, C. R., Bielefeldt-Ohmann, H., Tumpey, T. M., Sabourin, P. J., Long, J. P., García-Sastre, A., Tolnay, A.-E., Albrecht, R., Pyles, J. A., Olson, P. H., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813234106 · Cited by 361
Self-citationMordstein, M., Kochs, G., Dumoutier, L., Renauld, J., Paludan, S. R., Klucher, K. M., & Staeheli, P. (2008) · PLoS Pathogens · doi:10.1371/journal.ppat.1000151 · Cited by 326
Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent
Machado, F. S., Johndrow, J. E., Esper, L., Dias, A., Báfica, A. L. B., Serhan, C. N., & Aliberti, J. (2006) · Nature Medicine · doi:10.1038/nm1355 · Cited by 309
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
Perkins, L. E. L., & Swayne, D. E. (2001) · Veterinary Pathology · doi:10.1354/vp.38-2-149 · Cited by 287
Self-citationBáfica, A. L. B., Scanga, C. A., Serhan, C. N., Machado, F. S., White, S., Sher, A., & Aliberti, J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23949 · Cited by 251
Chest Radiographic and CT Findings in Novel Swine-Origin Influenza A (H1N1) Virus (S-OIV) Infection
Agarwal, P., Cinti, S. K., & Kazerooni, E. A. (2009) · American Journal of Roentgenology · doi:10.2214/ajr.09.3599 · Cited by 222
Cillóniz, C., Shinya, K., Peng, X., Korth, M. J., Proll, S. C., Aicher, L. D., Carter, V. S., Chang, J. H., Kobasa, D., Feldmann, F., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000604 · Cited by 210
Self-citationAliberti, J., Serhan, C. N., & Sher, A. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20021183 · Cited by 206
Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing
Svensson, C. I., Zattoni, M., & Serhan, C. N. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061826 · Cited by 175
MicroRNA Expression and Virulence in Pandemic Influenza Virus-Infected Mice
Yu, L., Chan, E. Y., Li, J., Ni, C., Peng, X., Rosenzweig, E., Tumpey, T. M., & Katze, M. G. (2010) · Journal of Virology · doi:10.1128/jvi.02203-09 · Cited by 166
Self-citationPerrone, L. A., Ahmad, A., Veguilla, V., Lu, X., Smith, G., Katz, J. M., Pushko, P., & Tumpey, T. M. (2009) · Journal of Virology · doi:10.1128/jvi.00207-09 · Cited by 143
Self-citationEarly Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice
Szretter, K. J., Gangappa, S., Belser, J. A., Zeng, H., Chen, H., Matsuoka, Y., Sambhara, S. R., Swayne, D. E., Tumpey, T. M., & Katz, J. M. (2009) · Journal of Virology · doi:10.1128/jvi.02144-08 · Cited by 103
Self-citationRegulation of apoptosis by type III interferons
Li, W., Lewis-Antes, A., Huang, J., Balan, M., & Kotenko, S. V. (2008) · Cell Proliferation · doi:10.1111/j.1365-2184.2008.00558.x · Cited by 101
Rubins, K., Hensley, L. E., Wahl‐Jensen, V., Daddario-DiCaprio, K. M., Young, H. A., Reed, D. S., Jahrling, P. B., Brown, P. O., Relman, D. A., & Geisbert, T. W. (2007) · Genome biology · doi:10.1186/gb-2007-8-8-r174 · Cited by 91
Disseminated Intravascular Coagulation (DIC)
Vohr, H.-W. (2015) · Springer eBooks · doi:10.1007/978-3-642-54596-2_200391 · Cited by 83
Karp, C. L., Flick, L. M., Yang, R., Uddin, J., & Petasis, N. A. (2005) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2005.05.015 · Cited by 41
Fighting the Flu with Inflammasome Signaling
Owen, D. M., & Gale, M. (2009) · Immunity · doi:10.1016/j.immuni.2009.03.011 · Cited by 35
de Jong, M. D. (2008) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e3181684d2d · Cited by 27
Smith, M. J., Clark, H. F., Lawley, D. A., Bell, L. M., Hodinka, R. L., DiStefano, D. J., Kulnis, G., Zaoutis, T. E., & Coffin, S. E. (2008) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e31814b279d · Cited by 24
Role of lipoxin in the modulation of immune response during infection
Machado, F. S., & Aliberti, J. (2008) · International Immunopharmacology · doi:10.1016/j.intimp.2008.01.001 · Cited by 17
Research works printed but not linked: 1
- Reed, L. J., and H. Muench. 1938. A simple method of estimating fifty percent endpoints. Am. J. Hyg.27:493-497.
Cited by
Sorted by citations
Pro-resolving lipid mediators are leads for resolution physiology
Serhan, C. N. (2014) · Nature · doi:10.1038/nature13479 · Cited by 3,041
Into the Eye of the Cytokine Storm
Tisoncik, J. R., Korth, M. J., Simmons, C. P., Farrar, J., Martin, T. R., & Katze, M. G. (2012) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.05015-11 · Cited by 1,940
Self-citationSpecialized pro-resolving mediators: endogenous regulators of infection and inflammation
Basil, M. C., & Levy, B. D. (2015) · Nature reviews. Immunology · doi:10.1038/nri.2015.4 · Cited by 832
The cytokine storm of severe influenza and development of immunomodulatory therapy
Liu, Q., Zhou, Y., & Yang, Z. (2015) · Cellular and Molecular Immunology · doi:10.1038/cmi.2015.74 · Cited by 725
The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution
Serhan, C. N., Chiang, N., & Dalli, J. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.03.004 · Cited by 583
Metadata
- Authors
- Cilloniz, C., Pantin-Jackwood, M. J., Ni, C., Goodman, A. G., Peng, X., Proll, S. C., Carter, V. S., Rosenzweig, E. R., Szretter, K. J., Katz, J. M., Korth, M. J., Swayne, D. E., Tumpey, T. M., & Katze, M. G.
- Affiliations
- Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195
- Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia 30606
- University of Washington (US)
- Washington University in St. Louis (US)
- Centers for Disease Control and Prevention (US)
- Agricultural Research Service (US)
- Corresponding author
- Katze, Michael G.
- ORCID
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2010-08
- Volume
- 84
- Issue
- 15
- Pages
- 7613-7624
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2897611
- OpenAlex
- W2130014663
- Cited by
- 136
- References
- 49
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 13 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 14 · 2014: 8 · 2013: 14 · 2012: 10
- FWCI
- 10.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (P01AI058113)
- 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
- H5N1 influenza virus, influenza pathogenesis, lung gene expression, inflammation, inflammasome, type I interferon, interferon receptor, viral dissemination, extrapulmonary infection, brain infection, host transcriptional response
- MeSH terms
- Animals, Female, Gene Expression Regulation, Inflammation, Lung, Orthomyxoviridae Infections, Virulence, Signal Transduction, Survival Analysis, Lipoxins, Mice, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H5N1 Subtype
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
