dc.contributor.author | Canton, Javier | |
dc.contributor.author | Fehr, Anthony R. | |
dc.contributor.author | Fernandez-Delgado, Raúl | |
dc.contributor.author | Gutierrez-Alvarez, Francisco J. | |
dc.contributor.author | Sanchez-Aparicio, Maria T. | |
dc.contributor.author | García-Sastre, Adolfo | |
dc.contributor.author | Perlman, Stanley | |
dc.contributor.author | Enjuanes, Luis | |
dc.contributor.author | Sola, Isabel | |
dc.date.accessioned | 2021-02-08T15:01:49Z | |
dc.date.available | 2021-02-08T15:01:49Z | |
dc.date.issued | 2018-01-25 | |
dc.identifier.citation | Canton J, Fehr AR, Fernandez-Delgado R, Gutierrez-Alvarez FJ, Sanchez-Aparicio MT, García-Sastre A, et al. (2018) MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection. PLoS Pathog 14(1): e1006838. https://doi.org/10.1371/journal.ppat.1006838 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/31385 | |
dc.description | This work is licensed under a Creative Commons Attribution 4.0 International License. | en_US |
dc.description.abstract | Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that emerged in 2012, causing severe pneumonia and acute respiratory distress syndrome (ARDS), with a case fatality rate of ~36%. When expressed in isolation, CoV accessory proteins have been shown to interfere with innate antiviral signaling pathways. However, there is limited information on the specific contribution of MERS-CoV accessory protein 4b to the repression of the innate antiviral response in the context of infection. We found that MERS-CoV 4b was required to prevent a robust NF-κB dependent response during infection. In wild-type virus infected cells, 4b localized to the nucleus, while NF-κB was retained in the cytoplasm. In contrast, in the absence of 4b or in the presence of cytoplasmic 4b mutants lacking a nuclear localization signal (NLS), NF-κB was translocated to the nucleus leading to the expression of pro-inflammatory cytokines. This indicates that NF-κB repression required the nuclear import of 4b mediated by a specific NLS. Interestingly, we also found that both in isolation and during infection, 4b interacted with α-karyopherin proteins in an NLS-dependent manner. In particular, 4b had a strong preference for binding karyopherin-α4 (KPNA4), which is known to translocate the NF-κB protein complex into the nucleus. Binding of 4b to KPNA4 during infection inhibited its interaction with NF-κB-p65 subunit. Thereby we propose a model where 4b outcompetes NF-κB for KPNA4 binding and translocation into the nucleus as a mechanism of interference with the NF-κB-mediated innate immune response. | en_US |
dc.publisher | Public Library of Science | en_US |
dc.rights | © 2018 Canton et al. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.title | MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Fehr, Anthony | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1371/journal.ppat.1006838 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-6556-5924 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-6551-1827 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-4213-2354 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-0854-0226 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-5704-1917 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess | en_US |