{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:08:53Z","timestamp":1793045333338,"version":"4.5.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31402163"],"award-info":[{"award-number":["31402163"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Committee of Science and Technology","award":["18DZ2293800"],"award-info":[{"award-number":["18DZ2293800"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diallyl trisulfide (DATS) is a garlic-derived organosulfur compound. As it has been shown to have anti-viral activity, we hypothesized that it may alleviate infections caused by H9N2 avian influenza virus (AIV), which is prevalent in poultry with pandemic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human lung A549 epithelial cells were treated with three different concentrations of DATS 24\u00a0h before (pre-treatment) or one hour after (post-treatment) H9N2 AIV infection. Culture supernatants were collected 24\u00a0h and 48\u00a0h post-infection and analyzed for viral titers and levels of inflammatory and anti-viral immune responses. For in vivo experiments, BABL\/c mice were administered daily by intraperitoneal injection with DATS (30\u00a0mg\/kg) for 2\u00a0weeks starting 1\u00a0day after H9N2 AIV infection. Clinical signs, lung pathology, and inflammatory and anti-viral immune responses were assessed 2, 4, and 6\u00a0days after infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both pre-treatment and post-treatment of A549 cells with DATS resulted in reduced viral loads, increased expression of anti-viral genes (RIG-I, IRF-3, and interferon-\u03b2), and decreased expression of inflammatory cytokines (TNF-\u03b1 and IL-6). These effects were also observed in H9N2 AIV-infected mice treated with DATS. Such treatment also reduced lung edema and inflammation in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Results suggest that DATS has anti-viral activity against H9N2 AIV and may be used as an alternative treatment for influenza virus infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12985-021-01641-w","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T06:18:41Z","timestamp":1629353921000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Antiviral activity of diallyl trisulfide against H9N2 avian influenza virus infection in vitro and in vivo"],"prefix":"10.1186","volume":"18","author":[{"given":"Le","family":"Ming","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guimei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"1641_CR1","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","volume":"391","author":"AD Iuliano","year":"2018","unstructured":"Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, Cohen C, Gran JM, Schanzer D, Cowling BJ, Wu P, Kyncl J, Ang LW, Park M, Redlberger-Fritz M, Yu H, Espenhain L, Krishnan A. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. The Lancet. 2018;391:1285\u2013300.","journal-title":"The Lancet"},{"key":"1641_CR2","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1038\/4371108a","volume":"437","author":"QM Le","year":"2005","unstructured":"Le QM, Kiso M, Someya K, Sakai YT, Nguyen TH, Nguyen KHL, Pham ND, Ngyen HH, Yamada S, Muramoto Y, Horimoto T, Takada A, Goto H, Suzuki T, Suzuki Y, Kawaoka Y. Avian flu: isolation of drug-resistant H5N1 virus. Nature. 2005;437:1108.","journal-title":"Nature"},{"key":"1641_CR3","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/S0140-6736(05)67338-2","volume":"366","author":"RA Bright","year":"2005","unstructured":"Bright RA, Medina MJ, Xu X, Perezoronoz G, Wallis TR, Davis XM, Povinelli L, Cox NJ, Klimov A. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet. 2005;366:1175\u201381.","journal-title":"Lancet"},{"key":"1641_CR4","doi-asserted-by":"publisher","first-page":"52","DOI":"10.2174\/138955751501150224160518","volume":"15","author":"SB Sharma","year":"2015","unstructured":"Sharma SB, Gupta R. Drug development from natural resource: a systematic approach. Mini-Rev Med Chem. 2015;15:52\u20137.","journal-title":"Mini-Rev Med Chem"},{"key":"1641_CR5","first-page":"1153","volume":"19","author":"J Fang","year":"2018","unstructured":"Fang J, Liu C, Wang Q, Lin P, Cheng F. In silico polypharmacology of natural products. Brief Bioinform. 2018;19:1153\u201371.","journal-title":"Brief Bioinform"},{"key":"1641_CR6","doi-asserted-by":"publisher","first-page":"79293","DOI":"10.1371\/journal.pone.0079293","volume":"8","author":"D Rajasekaran","year":"2013","unstructured":"Rajasekaran D, Palombo EA, ChiaYeo T, LimSiokLey D, LeeTu C, Malherbe F, Grollo L. Identification of traditional medicinal plant extracts with novel anti-influenza activity. PLoS ONE. 2013;8:79293.","journal-title":"PLoS ONE"},{"key":"1641_CR7","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.antiviral.2005.06.010","volume":"68","author":"S Jae-Min","year":"2005","unstructured":"Jae-Min S, Kwang-Hee L, Baik-Lin S. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res. 2005;68:66\u201374.","journal-title":"Antiviral Res"},{"key":"1641_CR8","doi-asserted-by":"publisher","first-page":"3665","DOI":"10.1021\/acs.jafc.7b00276","volume":"65","author":"R Li","year":"2017","unstructured":"Li R, Liu T, Liu M, Chen F, Liu S, Yang J. Anti-influenza A virus activity of dendrobine and its mechanism of action. J Agric Food Chem. 2017;65:3665\u201374.","journal-title":"J Agric Food Chem"},{"key":"1641_CR9","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.tifs.2020.08.006","volume":"104","author":"R Rouf","year":"2020","unstructured":"Rouf R, Uddin SJ, Sarker DK, Islam MT, Ali ES, Shilpi JA, Nahar L, Tiralongo E, Sarker SD. Anti-viral potential of garlic (Allium sativum) and it\u2019s organosulfur compounds: a systematic update of pre-clinical and clinical data. Trends Food Sci Technol. 2020;104:219\u201334.","journal-title":"Trends Food Sci Technol"},{"key":"1641_CR10","doi-asserted-by":"publisher","first-page":"2608","DOI":"10.5897\/AJMR12.2329","volume":"72","author":"P Mehrbod","year":"2013","unstructured":"Mehrbod P, Aini I, Amini E, Eslami M, Bande F. Assessment of direct immunofluorescence assay in detection of antiviral effect of garlic extract on influenza virus. Afr J Microbiol Res. 2013;72:2608\u201316.","journal-title":"Afr J Microbiol Res"},{"key":"1641_CR11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.21859\/isv.3.1.19","volume":"3","author":"P Mehrbod","year":"2009","unstructured":"Mehrbod P, Amini E, Tavassotikheiri M. Antiviral activity of garlic extract on influenza virus. Iran J Virol. 2009;3:19\u201323.","journal-title":"Iran J Virol"},{"key":"1641_CR12","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/401630","author":"R Arreola","year":"2015","unstructured":"Arreola R, Quintero-Fabi\u00e1n S, L\u00f3pez-Roa RI, Flores-Guti\u00e9rrez EO, Reyes-Grajeda JP, Carrera-Quintanar L, Ortu\u00f1o-Sahag\u00fan D. Immunomodulation and anti-Inflammatory effects of garlic compounds. J Immunol Res. 2015. https:\/\/doi.org\/10.1155\/2015\/401630.","journal-title":"J Immunol Res"},{"key":"1641_CR13","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3390\/v9070159","volume":"9","author":"A Hall","year":"2017","unstructured":"Hall A, Troupin A, Londono-Renteria B, Colpitts TM. Garlic organosulfur compounds reduce inflammation and oxidative stress during dengue virus infection. Viruses. 2017;9:159.","journal-title":"Viruses"},{"key":"1641_CR14","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.tifs.2007.07.011","volume":"8","author":"M Corzo-Mart\u00ednez","year":"2007","unstructured":"Corzo-Mart\u00ednez M, Corzo N, Villamiel M. Biological properties of onions and garlic. Trends Food Sci Technol. 2007;8:609\u201325.","journal-title":"Trends Food Sci Technol"},{"key":"1641_CR15","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1073\/pnas.82.6.1785","volume":"82","author":"JW Yewdell","year":"1985","unstructured":"Yewdell JW, Bennink JR, Smith GL, Moss B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci USA. 1985;82:1785\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1641_CR16","first-page":"3","volume":"20","author":"B Chen","year":"1994","unstructured":"Chen B, Zhang ZJ, Chen WB. Isolation and identification of avian influenza virus. Chin J Vet Med. 1994;20:3\u20135.","journal-title":"Chin J Vet Med"},{"key":"1641_CR17","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.virol.2005.06.025","volume":"340","author":"C Li","year":"2005","unstructured":"Li C, Yu K, Tian G, Yu D, Liu L, Jing B, Ping J, Chen H. Evolution of H9N2 influenza viruses from domestic poultry in Mainland China. Virology. 2005;340:70\u201383.","journal-title":"Virology"},{"key":"1641_CR18","doi-asserted-by":"publisher","first-page":"6988","DOI":"10.1128\/JVI.77.12.6988-6994.2003","volume":"77","author":"KS Li","year":"2003","unstructured":"Li KS, Xu KM, Peiris JS, Poon LL, Yu KZ, Yuen KY, Shortridge KF, Webster RG, Guan Y. Characterization of H9 subtype influenza viruses from the ducks of southern China: a candidate for the next influenza pandemic in humans? J Virol. 2003;77:6988\u201394.","journal-title":"J Virol"},{"key":"1641_CR19","doi-asserted-by":"publisher","first-page":"e1004508","DOI":"10.1371\/journal.ppat.1004508","volume":"10","author":"X Li","year":"2014","unstructured":"Li X, Shi J, Guo J, Deng G, Zhang Q, Wang J, He X, Wang K, Chen J, Li Y, Fan J, Kong H, Gu C, Guan Y, Suzuki Y, Kawaoka Y, Liu L, Jiang Y, Tian G, Li Y, Bu Z, Chen H. Genetics, receptor binding property, and transmissibility in mammals of naturally isolated H9N2 avian influenza viruses. PLoS Pathog. 2014;10:e1004508.","journal-title":"PLoS Pathog"},{"key":"1641_CR20","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1073\/pnas.1422456112","volume":"112","author":"J Pu","year":"2015","unstructured":"Pu J, Wang S, Yin Y, Zhang G, Carter RA, Wang J, Xu G, Sun H, Wen C, Wang D, Zhu B, Lemmon G, Jia Y, Duan S, Wang Q, Du Q, Sun M, Bao J, Sin Y, Zhao J, Zhang H, Wu G, Liu J, Webster RG. Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus. Proc Natl Acad Sci USA. 2015;112:548\u201353.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1641_CR21","doi-asserted-by":"publisher","first-page":"9372","DOI":"10.1128\/JVI.74.20.9372-9380.2000","volume":"74","author":"Y Guan","year":"2000","unstructured":"Guan Y, Shortridge KF, Krauss S, Chin PS, Dyrting KC, Ellis TM, Webster RG. Peiris M (2000) H9N2 influenza viruses possessing H5N1-like internal genomes continue to circulate in poultry in Southeastern China. J Virol. 2000;74:9372\u201380.","journal-title":"J Virol"},{"key":"1641_CR22","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/S0140-6736(14)60111-2","volume":"383","author":"H Chen","year":"2014","unstructured":"Chen H, Yuan H, Gao R, Zhang J, Wang D, Xiong Y, Fan G, Yang F, Li X, Zhou J, Zou S, Yang L, Chen T, Dong L, Bo H, Zhao X, Zhang Y, Lan Y, Bai T, Dong J, Li Q, Wang S, Zhang Y, Li H, Gong T, Shi Y, Ni X, Li J, Zhou J, Fan J, Wu J, Zhou X, Hu M, Wan J, Yang W, Li D, Wu G, Feng Z, Gao GF, Wang Y, Jin Q, Liu M, Shu Y. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet. 2014;383:714\u201321.","journal-title":"Lancet"},{"key":"1641_CR23","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.vetmic.2013.05.013","volume":"166","author":"G Zhu","year":"2013","unstructured":"Zhu G, Wang R, Xuan F, Daszak P, Anthony SJ, Zhang S, Zhang L, He G. Characterization of recombinant H9N2 influenza viruses isolated from wild ducks in China. Vet microbial. 2013;166:327\u201336.","journal-title":"Vet microbial"},{"key":"1641_CR24","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12985-017-0683-y","volume":"14","author":"B Gui","year":"2017","unstructured":"Gui B, Chen Q, Hu C, Zhu C, He G. Effects ofcalcitriol (1, 25-dihydroxy-vitamin D3) on the inflammatory response induced by H9N2 influenza virus infection in human lung A549 epithelial cells and in mice. Virol J. 2017;14:10.","journal-title":"Virol J"},{"key":"1641_CR25","first-page":"145","volume":"31","author":"E Ayaz","year":"2007","unstructured":"Ayaz E, Alpsoy HC. Garlic (Allium sativum) and traditional medicine. Turkiye Parazitol Derg. 2007;31:145\u20139.","journal-title":"Turkiye Parazitol Derg"},{"key":"1641_CR26","first-page":"768","volume-title":"Medicinal plants of South Asia","author":"R Rehman","year":"2019","unstructured":"Rehman R, Saif S, Hanif MA, Riaz M. Medicinal plants of South Asia. Amsterdam: Elsevier B. V; 2019. p. 768."},{"key":"1641_CR27","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s00421-008-0726-6","volume":"103","author":"P Peeling","year":"2008","unstructured":"Peeling P, Dawson B, Goodman C, Landers G, Trinder D. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol. 2008;103:381.","journal-title":"Eur J Appl Physiol"},{"key":"1641_CR28","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1189\/jlb.0509368","volume":"86","author":"J McGill","year":"2009","unstructured":"McGill J, Heusel JW, Legge KL. Innate immune control and regulation of influenza virus infections. J Leukoc Biol. 2009;86:803\u201312.","journal-title":"J Leukoc Biol"},{"key":"1641_CR29","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s00430-013-0317-y","volume":"203","author":"R Huang","year":"2014","unstructured":"Huang R, Liu J, Liang W, Wang A, Liu Z, Yang Y, Lv J, Bao Y, Gao Y, Miao Z. Response profiles of cytokines and chemokines against avian H9N2 influenza virus within the mouse lung. Med Microbiol Immunol. 2014;203:109\u201314.","journal-title":"Med Microbiol Immunol"},{"key":"1641_CR30","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2174\/1568009033333736","volume":"3","author":"M Thomson","year":"2003","unstructured":"Thomson M, Ali M. Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent. Curr Cancer Drug Tar. 2003;3:67\u201381.","journal-title":"Curr Cancer Drug Tar"},{"key":"1641_CR31","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1126\/science.1132998","volume":"314","author":"A Pichlmair","year":"2006","unstructured":"Pichlmair A, Schulz O, Tan CP, N\u00e4slund TI, Liljestr\u00f6m P, Weber F, Sousa CR. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5\u2019-phosphates. Science. 2006;314:997\u20131001.","journal-title":"Science"},{"key":"1641_CR32","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1126\/science.1132505","volume":"314","author":"V Hornung","year":"2006","unstructured":"Hornung V, Ellegast J, Kim S, Brz\u00f3zka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann KK, Schlee M, Endres S, Hartmann G. 5\u2019-Triphosphate RNA is the ligand for RIG-I. Science. 2006;314:994\u20137.","journal-title":"Science"},{"key":"1641_CR33","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1126\/science.2543070","volume":"244","author":"T Oda","year":"1989","unstructured":"Oda T, Akaike T, Hamamoto T, Suzuki F, Hirano T, Meada H. Oxygen radicals in influenzainduced pathogenesis and treatment with pyran polymer-conjugated SOD. Science. 1989;244:974\u20136.","journal-title":"Science"},{"key":"1641_CR34","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/1743-422X-7-93","volume":"7","author":"AT Washington","year":"2010","unstructured":"Washington AT, Singh G, Aiyar A. Diametrically opposed effects of hypoxia and oxidative stress on two viral transactivators. Virol J. 2010;7:93.","journal-title":"Virol J"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-021-01641-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-021-01641-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-021-01641-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T06:21:18Z","timestamp":1629354078000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/s12985-021-01641-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,19]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1641"],"URL":"https:\/\/doi.org\/10.1186\/s12985-021-01641-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-295808\/v1","asserted-by":"object"}]},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,19]]},"assertion":[{"value":"8 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments were conducted under biosafety level 2 conditions. Animals were maintained according to the National Institutes of Health (NIH) guidelines for the Care and Use of Experimental Animals. All animal experiments were performed according to established safety protocols and were approved by the Animal Ethics Committee of the East China Normal University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"171"}}