{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:49:04Z","timestamp":1790725744263,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Shanghai Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["No. 17ZR1437400"],"award-info":[{"award-number":["No. 17ZR1437400"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["no. 31772753, 31572543, 31700136 and 31702237"],"award-info":[{"award-number":["no. 31772753, 31572543, 31700136 and 31702237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Project of Shanghai Science and Technology Commission","award":["No. 17391901700"],"award-info":[{"award-number":["No. 17391901700"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The influenza A virus (IAV) is an important cause of respiratory disease worldwide. It is well known that alveolar epithelial cells are the target cells for the IAV, but there is relatively limited knowledge regarding the role of macrophages during IAV infection. Here, we aimed to analyze transcriptome differences in mouse lungs and macrophage (RAW264.7) cell lines infected with either A\/California\/04\/2009 H1N1 (CA09) or A\/chicken\/SD\/56\/2015 H9N2 (SD56) using deep sequencing. The uniquely differentially expressed genes (UDEGs) were analyzed with the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases; the results showed that the lungs infected with the two different viruses had different enrichments of pathways and terms. Interestingly, CA09 virus infection in mice was mostly involved with genes related to the extracellular matrix (ECM), while the most significant differences after SD56 infection in mice were in immune-related genes. Gene set enrichment analysis (GSEA) of RAW264.7 cells revealed that regulation of the cell cycle was of great significance after CA09 infection, whereas the regulation of the immune response was most enriched after SD56 infection, which was consistent with analysis results in the lung. Similar results were obtained from weighted gene co-expression network analysis (WGCNA), where cell cycle regulation was extensively activated in RAW264.7 macrophages infected with the CA09 virus. Disorder of the cell cycle is likely to affect their normal immune regulation, which may be an important factor leading to their different prognoses. These results provide insight into the mechanism of the CA09 virus that caused a pandemic and explain the different reactivities of monocytes\/macrophages infected by H9N2 and H1N1 IAV subtypes.<\/jats:p>","DOI":"10.3390\/v13102031","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:59:47Z","timestamp":1633917587000},"page":"2031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["RNA-Seq Analysis of Influenza A Virus-Induced Transcriptional Changes in Mice Lung and Its Possible Implications for the Virus Pathogenicity in Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3549-1072","authenticated-orcid":false,"given":"Tianxin","family":"Ma","sequence":"first","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdou","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Virology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanlong","family":"Xu","sequence":"additional","affiliation":[{"name":"China Institute of Veterinary Drug Control, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxiang","family":"Xin","sequence":"additional","affiliation":[{"name":"China Institute of Veterinary Drug Control, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danqi","family":"Bao","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Lu","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Niu","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihua","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaochao","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmei","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyang","family":"Teng","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zejun","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinfang","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"ref_1","first-page":"359","article-title":"Evolution and ecology of influenza A viruses","volume":"385","author":"Yoon","year":"2014","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Francis, M.E., King, M.L., and Kelvin, A.A. (2019). Back to the future for influenza preimmunity-looking back at influenza virus history to infer the outcome of future infections. Viruses, 11.","DOI":"10.3390\/v11020122"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0140-6736(17)30129-0","article-title":"Influenza","volume":"390","author":"Paules","year":"2017","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nature08182","article-title":"Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic","volume":"459","author":"Smith","year":"2009","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Brookes, S.M., Nunez, A., Choudhury, B., Matrosovich, M., Essen, S.C., Clifford, D., Slomka, M.J., Kuntz-Simon, G., Garcon, F., and Nash, B. (2010). Replication, pathogenesis and transmission of pandemic (H1N1) 2009 virus in non-immune pigs. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009068"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/nature08260","article-title":"In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses","volume":"460","author":"Itoh","year":"2009","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1128\/JVI.01619-09","article-title":"Pandemic H1N1 2009 influenza a virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons","volume":"84","author":"Pirhonen","year":"2010","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1007\/s00134-012-2565-5","article-title":"Elevation of creatine kinase is associated with worse outcomes in 2009 pH1N1 influenza A infection","volume":"38","author":"Borgatta","year":"2012","journal-title":"Intensive Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jiang, W., Liu, S., Hou, G., Li, J., Zhuang, Q., Wang, S., Zhang, P., and Chen, J. (2012). Chinese and global distribution of H9 subtype avian influenza viruses. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052671"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.1038\/s41467-020-19671-3","article-title":"Dominant subtype switch in avian influenza viruses during 2016\u20132019 in China","volume":"11","author":"Bi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13567-017-0453-2","article-title":"Current situation of H9N2 subtype avian influenza in China","volume":"48","author":"Gu","year":"2017","journal-title":"Vet. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1006\/viro.2000.0799","article-title":"H9N2 influenza A viruses from poultry in Asia have human virus-like receptor specificity","volume":"281","author":"Matrosovich","year":"2001","journal-title":"Virology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.virol.2017.08.028","article-title":"Insights into genetic diversity and biological propensities of potentially zoonotic avian influenza H9N2 viruses circulating in Egypt","volume":"511","author":"Naguib","year":"2017","journal-title":"Virology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.bbrc.2020.06.065","article-title":"The adaptability of H9N2 avian influenza A virus to humans: A comparative docking simulation study","volume":"529","author":"Xu","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1128\/JVI.02316-06","article-title":"Evolution and molecular epidemiology of H9N2 influenza A viruses from quail in southern China, 2000 to 2005","volume":"81","author":"Xu","year":"2007","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1128\/JCM.43.11.5760-5767.2005","article-title":"Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003","volume":"43","author":"Butt","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1099\/vir.0.82783-0","article-title":"Antigenic and genetic characterization of H9N2 swine influenza viruses in China","volume":"88","author":"Cong","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: A revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1093\/bioinformatics\/bti430","article-title":"Automated genome annotation and pathway identification using the KEGG Orthology (KO) as a controlled vocabulary","volume":"21","author":"Mao","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"Article17","DOI":"10.2202\/1544-6115.1128","article-title":"A general framework for weighted gene co-expression network analysis","volume":"4","author":"Zhang","year":"2005","journal-title":"Stat. Appl. Genet. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/B978-0-12-385118-5.00006-2","article-title":"Quantitative real-time PCR-based analysis of gene expression","volume":"500","author":"Jozefczuk","year":"2011","journal-title":"Methods Enzym."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.chom.2016.09.005","article-title":"Extracellular matrix proteolysis by MT1-MMP contributes to influenza-related tissue damage and mortality","volume":"20","author":"Altboum","year":"2016","journal-title":"Cell Host. Microbe."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"Theocharis","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.15252\/embr.201439246","article-title":"The extracellular matrix modulates the hallmarks of cancer","volume":"15","author":"Pickup","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1128\/JVI.02200-10","article-title":"Viral replication and innate host responses in primary human alveolar epithelial cells and alveolar macrophages infected with influenza H5N1 and H1N1 viruses","volume":"85","author":"Yu","year":"2011","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cellimm.2018.01.005","article-title":"Alveolar macrophages","volume":"330","author":"Joshi","year":"2018","journal-title":"Cell. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1136\/thoraxjnl-2017-210010","article-title":"Neutrophils drive alveolar macrophage IL-1\u03b2 release during respiratory viral infection","volume":"73","author":"Patel","year":"2018","journal-title":"Thorax"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1128\/JVI.03176-12","article-title":"Influenza A virus NS1 induces G0\/G1 cell cycle arrest by inhibiting the expression and activity of RhoA protein","volume":"87","author":"Jiang","year":"2013","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13038","DOI":"10.1111\/cmi.13038","article-title":"Influenza virus matrix protein M1 interacts with SLD5 to block host cell cycle","volume":"21","author":"Zhu","year":"2019","journal-title":"Cell Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43829","DOI":"10.1038\/srep43829","article-title":"IL-6 ameliorates acute lung injury in influenza virus infection","volume":"7","author":"Yang","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/2031\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:10:39Z","timestamp":1760166639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/2031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,8]]},"references-count":34,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["v13102031"],"URL":"https:\/\/doi.org\/10.3390\/v13102031","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,8]]}}}