{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T07:36:49Z","timestamp":1775029009620,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human infection with influenza A\/Hong Kong\/156\/97 (H5N1) avian influenza virus is associated with a high mortality rate of 60%. This virus is originated from influenza A\/Quail\/Hong Kong\/G1\/97 (H9N2\/G1) avian influenza virus. Since the 1990s, four lineages of H9N2 viruses have been circulating in poultry and cause occasional infection in humans in different countries. Due to its zoonotic and genetic reassortment potential, H9N2\/G1 and H5N1 viruses are believed to be the next pandemic candidates. Previous reports, including ours, showed that the virulence of avian virus strains correlates with their ability to dysregulate cytokine expression, including TNF-\u03b1, CXCL10, and related chemokines in the virus-infected cells. However, the transcriptional factors required for this cytokine dysregulation remains undefined. In light of our previous report showing the unconventional role of MYC, an onco-transcriptional factor, for regulating the antibacterial responses, we hypothesize that the influenza virus\u2013induced cytokine productions may be governed by MYC\/MAX\/MXD1 network members. Here, we demonstrated that the influenza A\/Hong Kong\/54\/98 (H1N1)- or H9N2\/G1 virus\u2013induced CXCL10 expressions can be significantly attenuated by knocking down the MXD1 expression in primary human blood macrophages. Indeed, only the MXD1 expression was up-regulated by both H1N1 and H9N2\/G1 viruses, but not other MYC\/MAX\/MXD1 members. The MXD1 expression and the CXCL10 hyperinduction were dependent on MEK1\/2 activation. By using EMSAs, we revealed that MXD1 directly binds to the CXCL10 promoter\u2013derived oligonucleotides upon infection of both viruses. Furthermore, silencing of MXD1 decreased the replication of H9N2 but not H1N1 viruses. Our results provide a new insight into the role of MXD1 for the pathogenicity of avian influenza viruses.<\/jats:p>","DOI":"10.1002\/jlb.4ma0620-703rr","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T04:50:37Z","timestamp":1597380637000},"page":"1631-1640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["MXD1 regulates the H9N2 and H1N1 influenza A virus\u2013induced chemokine expression and their replications in human macrophage"],"prefix":"10.1093","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2076-4361","authenticated-orcid":true,"given":"Howard C H","family":"Yim","sequence":"first","affiliation":[{"name":"Microbiome Research Centre, St George and Sutherland Clinical School, The University of New South Wales , Sydney , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas Y Y","family":"Leon","sequence":"additional","affiliation":[{"name":"Dr. Li Dak-Sum Research Centre, The University of Hong Kong , Pok Fu Lam, Hong Kong Special Administrative Region , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7156-0318","authenticated-orcid":true,"given":"James C B","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pok Fu Lam, Hong Kong Special Administrative Region , P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"key":"2023032108055009700_jlb10761-cit-0001","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s11262-009-0404-8","article-title":"An update on swine-origin influenza virus A\/H1N1: a review","volume":"39","author":"Schnitzler","year":"2009","journal-title":"Virus Genes"},{"key":"2023032108055009700_jlb10761-cit-0002","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0002-y","article-title":"Influenza","volume":"4","author":"Krammer","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"2023032108055009700_jlb10761-cit-0003","doi-asserted-by":"crossref","DOI":"10.3390\/vetsci5040082","article-title":"The multifaceted zoonotic risk of H9N2 avian influenza","volume":"5","author":"Pusch","year":"2018","journal-title":"Veterinary 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