{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:06:26Z","timestamp":1792155986472,"version":"4.4.0"},"reference-count":87,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI147187"],"award-info":[{"award-number":["R21 AI147187"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 GM137801"],"award-info":[{"award-number":["R35 GM137801"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Long noncoding RNAs (lncRNAs) are a newer class of noncoding transcripts identified as key regulators of biological processes. Here, we aimed to identify novel lncRNA targets that play critical roles in major human respiratory viral infections by systematically mining large-scale transcriptomic data sets. Using bulk RNA-sequencing (RNA-seq) analysis, we identified a previously uncharacterized lncRNA, named virus-inducible lncRNA modulator of interferon response (\n                      <jats:italic>VILMIR<\/jats:italic>\n                      ), that was consistently upregulated after\n                      <jats:italic>in vitro<\/jats:italic>\n                      influenza infection across multiple human epithelial cell lines and influenza A virus subtypes.\n                      <jats:italic>VILMIR<\/jats:italic>\n                      was also upregulated after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) infections\n                      <jats:italic>in vitro<\/jats:italic>\n                      . We experimentally confirmed the response of\n                      <jats:italic>VILMIR<\/jats:italic>\n                      to influenza infection and interferon-beta (IFN-\u03b2) treatment in the A549 human epithelial cell line and found the expression of\n                      <jats:italic>VILMIR<\/jats:italic>\n                      was robustly induced by IFN-\u03b2 treatment in a dose- and time-specific manner. Single-cell RNA-seq analysis of bronchoalveolar lavage fluid samples from coronavirus disease 2019 (COVID-19) patients uncovered that\n                      <jats:italic>VILMIR<\/jats:italic>\n                      was upregulated across various cell types, including at least five immune cells. The upregulation of\n                      <jats:italic>VILMIR<\/jats:italic>\n                      in immune cells was further confirmed in the human T cell and monocyte cell lines, SUP-T1 and THP-1, after IFN-\u03b2 treatment. Finally, we found that knockdown of\n                      <jats:italic>VILMIR<\/jats:italic>\n                      expression reduced the magnitude of host transcriptional responses to both IFN-\u03b2 treatment and influenza A virus infection in A549 cells. Together, our results show that\n                      <jats:italic>VILMIR<\/jats:italic>\n                      is a novel interferon-stimulated gene (ISG) that regulates the host interferon response and may be a potential therapeutic target for human respiratory viral infections upon further mechanistic investigation.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Identifying host factors that regulate the immune response to human respiratory viral infection is critical to developing new therapeutics. Human long noncoding RNAs (lncRNAs) have been found to play key regulatory roles during biological processes; however, the majority of lncRNA functions within the host antiviral response remain unknown. In this study, we identified that a previously uncharacterized lncRNA, virus-inducible lncRNA modulator of interferon response (\n                        <jats:italic>VILMIR<\/jats:italic>\n                        ), is upregulated after major respiratory viral infections including influenza, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus. We demonstrated that\n                        <jats:italic>VILMIR<\/jats:italic>\n                        is an interferon-stimulated gene that is upregulated after interferon-beta (IFN-\u03b2) in several human cell types. We also found that knockdown of\n                        <jats:italic>VILMIR<\/jats:italic>\n                        reduced the magnitude of host transcriptional responses to IFN-\u03b2 treatment and influenza A infection in human epithelial cells. Our results reveal that\n                        <jats:italic>VILMIR<\/jats:italic>\n                        regulates the host interferon response and may present a new therapeutic target during human respiratory viral infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00141-25","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T10:57:42Z","timestamp":1742900262000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Human long noncoding RNA\n                    <i>VILMIR<\/i>\n                    is induced by major respiratory viral infections and modulates the host interferon response"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1621-7370","authenticated-orcid":true,"given":"Kristen","family":"John","sequence":"first","affiliation":[{"name":"Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]},{"name":"Genetics & Genomics Graduate Program, North Carolina State University","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Huntress","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]},{"name":"Bioinformatics Graduate Program, North Carolina State University","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8897-2143","authenticated-orcid":true,"given":"Ethan","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]},{"name":"Bioinformatics Graduate Program, North Carolina State University","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsuan","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7193-8456","authenticated-orcid":true,"given":"Tammy S.","family":"Tollison","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7197-9952","authenticated-orcid":false,"given":"Sergio","family":"Covarrubias","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz","place":["Santa Cruz, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4235-8508","authenticated-orcid":true,"given":"Elisa","family":"Crisci","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5600-5404","authenticated-orcid":false,"given":"Susan","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz","place":["Santa Cruz, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0117-3582","authenticated-orcid":true,"given":"Xinxia","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]},{"name":"Bioinformatics Graduate Program, North Carolina State University","place":["Raleigh, USA"]},{"name":"Bioinformatics Research Center, North Carolina State University","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003569"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11233"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00566-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1087"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.020"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12943"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00315-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines5040037"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2019.194419"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.07.005"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00206-10"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.4161\/rna.29442"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1778429"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00786-19"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00539-18"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.4161\/rna.27504"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.036"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/v10060330"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao0409"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1193"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-4330-1"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3542"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.06.009"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.047"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00085-16"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00518-18"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-017-0036-x"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01920-08"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.026"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86002-x"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0527-6"},{"key":"e_1_3_4_38_2","volume-title":"Manual for the laboratory diagnosis and virological surveillance of influenza","author":"Organization WH","year":"2011","unstructured":"Organization WH. 2011. Manual for the laboratory diagnosis and virological surveillance of influenza. World Health Organization, Geneva."},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.4.937-943.1999"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a118408"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.03.048"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.799155"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3437"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07901-8"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0901-9"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac958"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2","author":"Wickham H","year":"2016","unstructured":"Wickham H, Sievert C. 2016. ggplot2. 2nd ed. Springer, Cham, Switzerland.","edition":"2"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1196"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.229102"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab959"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.02.008"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz087"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01369-0"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02323-08"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1062"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.606456"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3581"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.028"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2019.10.004"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0778-x"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01159-19"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1105309"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108586"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1035-6"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00635-21"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10030303"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.517461"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2017.04.009"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12127"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0888-2_10"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012854"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00655"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.670177"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01186"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25483"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1240925"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01956-12"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2198"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2011.10.008"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9738"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.165936"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008144"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2019.05.003"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00141-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00141-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T09:04:20Z","timestamp":1744707860000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00141-25"}},"subtitle":[],"editor":[{"given":"Tom","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,15]]},"references-count":87,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,15]]}},"alternative-id":["10.1128\/jvi.00141-25"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00141-25","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.03.25.586578","asserted-by":"object"}]},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,15]]},"assertion":[{"value":"2025-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00141-25"}}