{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:29:51Z","timestamp":1790270991287,"version":"4.1.0"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI091797"],"award-info":[{"award-number":["R01AI091797"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007765","name":"Kansas State University","doi-asserted-by":"publisher","award":["Start-up funds"],"award-info":[{"award-number":["Start-up funds"]}],"id":[{"id":"10.13039\/100007765","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21AI127404"],"award-info":[{"award-number":["R21AI127404"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Although influenza A virus (IAV) evades cellular defense systems to effectively propagate in the host, the viral immune-evasive mechanisms are incompletely understood. Our recent data showed that hemagglutinin (HA) of IAV induces degradation of type I IFN receptor 1 (IFNAR1). Here, we demonstrate that IAV HA induces degradation of type II IFN (IFN-\u03b3) receptor 1 (IFNGR1), as well as IFNAR1, via casein kinase 1\u03b1 (CK1\u03b1), resulting in the impairment of cellular responsiveness to both type I and II IFNs. IAV infection or transient HA expression induced degradation of both IFNGR1 and IFNAR1, whereas HA gene-deficient IAV failed to downregulate the receptors. IAV HA caused the phosphorylation and ubiquitination of IFNGR1, leading to the lysosome-dependent degradation of IFNGR1. Influenza viral HA strongly decreased cellular sensitivity to type II IFNs, as it suppressed the activation of STAT1 and the induction of IFN-\u03b3-stimulated genes in response to exogenously supplied recombinant IFN-\u03b3. Importantly, CK1\u03b1, but not p38 MAP kinase or protein kinase D2, was proven to be critical for HA-induced degradation of both IFNGR1 and IFNAR1. Pharmacologic inhibition of CK1\u03b1 or small interfering RNA (siRNA)-based knockdown of CK1\u03b1 repressed the degradation processes of both IFNGR1 and IFNAR1 triggered by IAV infection. Further, CK1\u03b1 was shown to be pivotal for proficient replication of IAV. Collectively, the results suggest that IAV HA induces degradation of IFN receptors via CK1\u03b1, creating conditions favorable for viral propagation. Therefore, the study uncovers a new immune-evasive pathway of influenza virus.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Influenza A virus (IAV) remains a grave threat to humans, causing seasonal and pandemic influenza. Upon infection, innate and adaptive immunity, such as the interferon (IFN) response, is induced to protect hosts against IAV infection. However, IAV seems to be equipped with tactics to evade the IFN-mediated antiviral responses, although the detailed mechanisms need to be elucidated. In the present study, we show that IAV HA induces the degradation of the type II IFN receptor IFNGR1 and thereby substantially attenuates cellular responses to IFN-\u03b3. Of note, a cellular kinase, casein kinase 1\u03b1 (CK1\u03b1), is crucial for IAV HA-induced degradation of both IFNGR1 and IFNAR1. Accordingly, CK1\u03b1 is proven to positively regulate IAV propagation. Thus, this study unveils a novel strategy employed by IAV to evade IFN-mediated antiviral activities. These findings may provide new insights into the interplay between IAV and host immunity to impact influenza virus pathogenicity.\n          <\/jats:p>","DOI":"10.1128\/jvi.00006-18","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T08:33:50Z","timestamp":1516005230000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Casein Kinase 1\u03b1 Mediates the Degradation of Receptors for Type I and Type II Interferons Caused by Hemagglutinin of Influenza A Virus"],"prefix":"10.1128","volume":"92","author":[{"given":"Chuan","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuvanthi","family":"Vijayan","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb J.","family":"Studstill","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine\/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bumsuk","family":"Hahm","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Missouri, Columbia, Missouri, USA"},{"name":"Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)11212-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403212101"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61171-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03122-15"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12012-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.07.039"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.294"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/598989"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu447"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.008"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200206000-00008"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2164(10)73004-5"},{"key":"e_1_3_2_14_2","first-page":"41","article-title":"Type I interferon: the ever unfolding story","volume":"316","author":"Pitha PM","year":"2007","unstructured":"Pitha PM, Kunzi MS. 2007. 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