{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:30:15Z","timestamp":1787329815040,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470967"],"award-info":[{"award-number":["32470967"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32571131"],"award-info":[{"award-number":["32571131"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2024JC\u2010YBMS\u2010692"],"award-info":[{"award-number":["2024JC\u2010YBMS\u2010692"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Psychological stress is a pervasive yet poorly understood modulator of infectious disease outcomes. Here, we report a mechanistic link between chronic stress and severe viral pathogenesis, identifying the \u03b22\u2010adrenergic receptor (\u03b22\u2010AR) as a critical host factor and therapeutic target. Using a model of chronic restraint stress and cowpox virus (CPXV) infection, we demonstrate that psychological stress significantly exacerbates disease severity and mortality. This increased susceptibility is driven by autophagy\u2010mediated downregulation of \u03b22\u2010AR, a process that is recapitulated during viral infection. Accordingly, genetic loss\u2010of\u2010function and pharmacological approaches established \u03b22\u2010AR as a critical host protective factor that suppresses CPXV replication. Leveraging this pathway, we identify the natural alkaloid lycorine as a novel \u03b22\u2010AR\u2010stabilizing ligand that rescues the receptor from degradation. Lycorine exhibits potent antiviral activity by suppressing post\u2010entry viral replication. In vivo, lycorine reduced viral burden and tissue pathology and improved survival following CPXV infection, and these protective effects required cluster of differentiation 8\u2010positive (CD8\n                    <jats:sup>+<\/jats:sup>\n                    ) T cells. Mechanistically, lycorine attenuates virus\u2010induced TANK\u2010 binding kinase 1\/interferon regulatory factor 3 (TBK1\/IRF3)associated inflammatory signaling while enhancing antiviral Interferon (IFN)\/interferon\u2010stimulated gene (ISG) responses through \u03b22\u2010AR\u2010associated and additional stimulator of interferon gene (STING)\u2010independent regulatory mechanisms. Collectively, our findings reveal \u03b22\u2010AR as a molecular link between psychological stress and antiviral immunity and highlight lycorine\u2010mediated \u03b22\u2010AR stabilization as a potential host\u2010directed antiviral strategy for poxvirus infection.\n                  <\/jats:p>","DOI":"10.1002\/advs.77306","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:35:02Z","timestamp":1787326502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting \u03b22\u2010Adrenergic Receptor Stability With Lycorine Reveals a Host\u2010Directed Pathway for Antiviral Defense Against Poxviruses"],"prefix":"10.1002","author":[{"given":"Xin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"},{"name":"National Local Joint Engineering Research Center for Precision Surgery &amp; Regenerative Medicine the First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenwen","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huini","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiao","family":"Huang","sequence":"additional","affiliation":[{"name":"National Local Joint Engineering Research Center for Precision Surgery &amp; Regenerative Medicine the First Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"},{"name":"School of Future Technology Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9989-7455","authenticated-orcid":false,"given":"Faiza","family":"Atique","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Translational Medicine Institute School of Basic Medical Sciences Health Science Center Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingli","family":"He","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1006-7893","authenticated-orcid":false,"given":"Zhijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01690-1"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0010141"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6710a5"},{"key":"e_1_2_11_5_1","unstructured":"WHO. 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