The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-κB
Open accessAbstract
High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-kappaB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-kappaB element on the promoter. We also showed that N protein activated IL-6 expression through NF-kappaB by facilitating the translocation of NF-kappaB from cytosol to nucleus. Mutational analyses revealed that two regions of N protein were essential for its function in the activation of IL-6. These results provided new insights into understanding the mechanism involved in the function of SARS-CoV N protein and pathogenesis of the virus.
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“In addition to this PRR-mediated activation of NF-κB, the nucleocapsid protein of SARS-CoV-1 activates IL-6 expression through NF-κB by facilitating the translocation of NF-κB from the cytosol to the nucleus (341).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [341]
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Cites
2 retracted
Yan, X., Qian, H., Mu, Y., Timani, K. A., Ye, L., Zhu, Y., & Wu, J. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.02.003 · Cited by 134 · cited 2×
“Our recent results indicated that N protein activates COX-2 gene expression by binding either directly or indirectly to NF-κB and C/EBP regulatory elements on COX-2 promoter (Yan et al., 2006).”
BackgroundMethodSelf-citationRetractedLiu, M., Yang, Y., Gu, C., Yue, Y., Wu, K. K., Wu, J., & Zhu, Y. (2007) · The FASEB Journal · doi:10.1096/fj.06-6589com · Cited by 81
Self-citationRetractedCharacterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome
Rota, P. A., Oberste, M. S., Monroe, S. S., Nix, W. A., Campagnoli, R. P., Icenogle, J. P., Peñaranda, S., Bankamp, B., Maher, K., Chen, M., et al. (2003) · Science · doi:10.1126/science.1085952 · Cited by 2,477 · cited 1×
“The N protein of SARS-CoV is 422 amino acids long, sharing only 20–30% homology with the N proteins of other coronaviruses (Marra et al., 2003; Rota et al., 2003).”
BackgroundSelf-citationThe Genome Sequence of the SARS-Associated Coronavirus
Marra, M. A., Jones, S. J. M., Astell, C. R., Holt, R. A., Brooks-Wilson, A. R., Butterfield, Y. S. N., Khattra, J. S., Asano, J. K., Barber, S., Chan, S. Y., et al. (2003) · Science · doi:10.1126/science.1085953 · Cited by 2,027 · cited 6×
“The N protein of SARS-CoV is 422 amino acids long, sharing only 20-30% homology with the N proteins of other coronaviruses (Marra et al., 2003; Rota et al., 2003) .”
BackgroundInfluentialInducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism
Sen, R., & Baltimore, D. (1986) · Cell · doi:10.1016/0092-8674(86)90807-x · Cited by 1,961 · cited 1×
“NF-κB belongs to the Rel family of transcription factors that form homo- or heterodimers through the Rel homology domain (Akira and Kishimoto, 1997; Sen and Baltimore, 1986).”
BackgroundVan Snick, J. (1990) · Annual Review of Immunology · doi:10.1146/annurev.iy.08.040190.001345 · Cited by 1,890 · cited 1×
“IL-6 is a pleiotropic cytokine that plays a major role in the host's response to injury or infection (Snick, 1990).”
BackgroundRel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.Preprint
Verma, I. M., Stevenson, J. K., Schwarz, E. M., Antwerp, D. V., & Miyamoto, S. (1995) · Genes & Development · doi:10.1101/gad.9.22.2723 · Cited by 1,696 · cited 1×
“In most cells, NF-κB is present in the cytoplasm bound to a member of the IκB family of inhibitors (Verma et al., 1995; Carlotti et al., 2000).”
BackgroundActivation of Interleukin-6 Gene Expression through the NF-κB Transcription Factor
Libermann, T. A., & Baltimore, D. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.5.2327 · Cited by 1,403 · cited 1×
“IL-6 gene activation involves the rapid transport of preexisting p65 to the nucleus after release from a complex with IκB in the cytosol (Lieberman and Baltimore, 1990) .”
BackgroundInterleukin-6 in Biology and Medicine
Akira, S., Taga, T., & Kishimoto, T. (1993) · Advances in immunology · doi:10.1016/s0065-2776(08)60532-5 · Cited by 1,402 · cited 2×
“Interleukin-6 (IL-6) is a pleiotropic cytokine that plays major roles in immunological responses, inflammation, bone metabolism, neoplasia, and aging (Akira et al., 1993; Papanicolaou et al., 1998; Erschler and Keller, 2000).”
BackgroundThe Severe Acute Respiratory Syndrome
Peiris, J. S. M., Yuen, K., Osterhaus, A. D. M. E., & Stöhr, K. (2003) · New England Journal of Medicine · doi:10.1056/nejmra032498 · Cited by 1,394
Cited by
Sorted by citations
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453
“In addition to this PRR-mediated activation of NF-κ B, the nucleo-capsid protein of SARS-CoV-1 activates IL-6 expression through NF-κ B by facilitating the translocation of NF-κ B from the cytosol to the nucleus (341).”
BackgroundNetland, J., Meyerholz, D. K., Moore, S., Cassell, M., & Perlman, S. (2008) · Journal of Virology · doi:10.1128/jvi.00737-08 · Cited by 1,293
“SARS-CoV products, such as the N protein, may directly induce IL-6 ( 55 ).”
BackgroundHost Factors in Coronavirus Replication
de Wilde, A. H., Snijder, E. J., Kikkert, M., & van Hemert, M. J. (2017) · Current topics in microbiology and immunology · doi:10.1007/82_2017_25 · Cited by 554
“2007; Song et al.”
BackgroundInfluentialRussell, B. A., Moss, C. L., George, G., Santaolalla, A., Cope, A. P., Papa, S., & Hemelrijck, M. V. (2020) · ecancermedicalscience · doi:10.3332/ecancer.2020.1022 · Cited by 440
“Following in vitro analysis, Yang et al [48] suggests the use of a combination therapy for SARS-CoV or MERS-CoV, wherein a tylophorine compound known to target transmissible gastroenteritis virus and a JAK2 inhibitor synergise to block the alternative dominant NF-κB activation mediated by JAK2.”
MethodDeDiego, M. L., Nieto-Torres, J. L., Regla-Nava, J. Á., Jiménez-Guardeño, J. M., Fernández‐Delgado, R., Fett, C., Castaño-Rodríguez, C., Perlman, S. M., & Enjuanes, L. (2013) · Journal of Virology · doi:10.1128/jvi.02576-13 · Cited by 395
Metadata
- Authors
- Zhang, X., Wu, K., Wang, D., Yue, X., Song, D., Zhu, Y., & Wu, J.
- Affiliations
- Wuhan University (CN)
- Guangxi Normal University (CN)
- Corresponding author
- Wu, Kailang
- Zhu, Ying
- Wu, Jianguo
- Venue
- Virology
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 365
- Issue
- 2
- Pages
- 324-335
- ISSN
- 0042-6822 (ISSN-L)
- PMC
- PMC7103332
- OpenAlex
- W2001975441
- Cited by
- 141
- References
- 43
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 19 · 2021: 26 · 2020: 43 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 1
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30470087)
- Major State Basic Research Development Program of China (2005CB522901)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV, nucleocapsid protein, interleukin-6, NF-κB, transcriptional activation, promoter regulation, NF-κB nuclear translocation, viral pathogenesis, SARS
- MeSH terms
- Coronavirus Nucleocapsid Proteins, Cell Line, Cell Nucleus, Cytoplasm, Epithelial Cells, Humans, Luciferases, Lung, Mutation, Protein Binding, Interleukin-6, NF-kappa B, Sequence Deletion, Genes, Reporter, Nucleocapsid Proteins, Artificial Gene Fusion, Protein Transport, Electrophoretic Mobility Shift Assay, Severe acute respiratory syndrome-related coronavirus, Immunoprecipitation
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