{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:26:12Z","timestamp":1773833172218,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but \"cytokine storm\" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Presentation of the hypothesis<\/jats:title><jats:p>Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Testing the hypothesis<\/jats:title><jats:p>CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in<jats:italic>vivo<\/jats:italic>and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Implications of the hypothesis<\/jats:title><jats:p>CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1743-422x-7-30","type":"journal-article","created":{"date-parts":[[2010,2,9]],"date-time":"2010-02-09T19:15:14Z","timestamp":1265742914000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior"],"prefix":"10.1186","volume":"7","author":[{"given":"Chuanfu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leili","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yansong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liuyu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Tomlinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuelin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbin","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,2,9]]},"reference":[{"key":"775_CR1","unstructured":"Kamps BS, Hoffmann C, Preiser W: Influenza Report 2006. Flying Publisher; 18."},{"key":"775_CR2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3201\/eid1209.05-0979","volume":"12","author":"J Taubenberger","year":"2006","unstructured":"Taubenberger J, Morens D: The 1918 Influenza: the mother of all pandemics. Emerg Infect Dis 2006, 12: 15-22.","journal-title":"Emerg Infect Dis"},{"key":"775_CR3","unstructured":"[http:\/\/www.who.int\/csr\/don\/2009_12_23\/en\/index.html]"},{"key":"775_CR4","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1126\/science.2543070","volume":"26","author":"T Oda","year":"1989","unstructured":"Oda T, Akaike T, Hamamoto T, Suzuki F, Hirano T, Maeda H: Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD. Science 1989, 26: 974-976. 10.1126\/science.2543070","journal-title":"Science"},{"key":"775_CR5","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1086\/649785","volume":"201","author":"PC Woo","year":"2010","unstructured":"Woo PC, Tung ET, Chan KH, Lau CC, Lau SK, Yuen KY: Cytokine Profiles Induced by the Novel Swine-Origin Influenza A\/H1N1 Virus: Implications for Treatment Strategies. J Infect Dis 2010, 201: 346-353. 10.1086\/649785","journal-title":"J Infect Dis"},{"key":"775_CR6","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/path.2417","volume":"216","author":"R Deng","year":"2008","unstructured":"Deng R, Lu M, Korteweg C, Gao Z, McNutt MA, Ye J, Zhang T, Gu J: Distinctly different expression of cytokines and chemokines in the lungs of two H5N1 avian influenza patients. J Pathol 2008, 216: 328-36. 10.1002\/path.2417","journal-title":"J Pathol"},{"key":"775_CR7","first-page":"365","volume":"42","author":"D Us","year":"2008","unstructured":"Us D: Cytokine storm in avian influenza. Mikrobiyol Bul 2008, 42: 365-80.","journal-title":"Mikrobiyol Bul"},{"key":"775_CR8","doi-asserted-by":"publisher","first-page":"8091","DOI":"10.1073\/pnas.0711942105","volume":"105","author":"BJ Zheng","year":"2008","unstructured":"Zheng BJ, Chan KW, Lin YP, Zhao GY, Chan C, Zhang HJ, Chen HL, Wong SS, Lau SK, 8 Woo PC, Chan KH, Jin DY, Yuen KY: Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A\/H5N1 virus. Proc Natl Acad Sci 2008, 105: 8091-8096. 10.1073\/pnas.0711942105","journal-title":"Proc Natl Acad Sci"},{"key":"775_CR9","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.immuni.2009.02.005","volume":"30","author":"IC Allen","year":"2009","unstructured":"Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, Guthrie EH, Pickles RJ, Ting JP: The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 2009, 30: 556-565. 10.1016\/j.immuni.2009.02.005","journal-title":"Immunity"},{"key":"775_CR10","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/nature05495","volume":"445","author":"D Kobasa","year":"2007","unstructured":"Kobasa D, Jones SM, Shinya K, Kash JC, Copps J, Ebihara H, Hatta Y, Kim JH, Halfmann P, Hatta M, Feldmann F, Alimonti JB, Fernando L, Li Y, Katze MG, Feldmann H, Kawaoka Y: Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 2007, 445: 319-323. 10.1038\/nature05495","journal-title":"Nature"},{"key":"775_CR11","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1038\/nm0805-821","volume":"11","author":"J Nicholls","year":"2005","unstructured":"Nicholls J, Peiris M: Good ACE, bad ACE do battle in lung injury, SARS. Nat Med 2005, 11: 821-822. 10.1038\/nm0805-821","journal-title":"Nat Med"},{"key":"775_CR12","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature03712","volume":"436","author":"Y Imai","year":"2005","unstructured":"Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM: Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005, 436: 112-116. 10.1038\/nature03712","journal-title":"Nature"},{"key":"775_CR13","doi-asserted-by":"publisher","first-page":"3846","DOI":"10.1128\/JVI.79.6.3846-3850.2005","volume":"79","author":"EC Mossel","year":"2005","unstructured":"Mossel EC, Huang C, Narayanan K, Makino S, Tesh RB, Peters CJ: Exogenous ACE2 expression allows refractory cell lines to support severe acute respiratory syndrome coronavirus replication. J Virol 2005, 79: 3846-3850. 10.1128\/JVI.79.6.3846-3850.2005","journal-title":"J Virol"},{"key":"775_CR14","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1056\/NEJM200104123441506","volume":"344","author":"MJ Walport","year":"2001","unstructured":"Walport MJ: Complement. Second of two parts. N Engl J Med 2001, 344: 1140-1144. 10.1056\/NEJM200104123441506","journal-title":"N Engl J Med"},{"key":"775_CR15","doi-asserted-by":"publisher","first-page":"3046","DOI":"10.1016\/j.vaccine.2007.12.003","volume":"26","author":"H Stoiber","year":"2008","unstructured":"Stoiber H, Banki Z, Wilflingseder D, Dierich MP: Complement-HIV interactions during all steps of viral pathogenesis. Vaccine 2008, 26: 3046-3054. 10.1016\/j.vaccine.2007.12.003","journal-title":"Vaccine"},{"key":"775_CR16","first-page":"365","volume":"3","author":"Z Blach-Olszewskal","year":"2007","unstructured":"Blach-Olszewska1 Z, Leszek J: Mechanisms of over-activated innate immune system regulation in autoimmune and neurodegenerative disorders. Neuropsychiatr Dis Treat 2007, 3: 365-372.","journal-title":"Neuropsychiatr Dis Treat"},{"key":"775_CR17","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1172\/JCI17348","volume":"111","author":"HB Song","year":"2003","unstructured":"Song HB, He C, Knaak C, Guthridge MJ, Holers VM, Tomlinson S: Complement receptor 2-mediated targeting of complement inhibitors to sites of complement activation. J Clin Invest 2003, 111: 1875-1885.","journal-title":"J Clin Invest"},{"key":"775_CR18","doi-asserted-by":"publisher","first-page":"7860","DOI":"10.4049\/jimmunol.179.11.7860","volume":"179","author":"HB Song","year":"2007","unstructured":"Song HB, Qiao F, Atkinson C, Holers VM, Tomlinson S: A complement C3 inhibitor specifically targeted to sites of complement activation effectively ameliorates collagen-induced arthritis in DBA\/1J mice. J Immunol 2007, 179: 7860-7867.","journal-title":"J Immunol"},{"key":"775_CR19","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nm0402-373","volume":"8","author":"M Kopf","year":"2002","unstructured":"Kopf M, Abel B, Gallimore A, Carroll M, Bachmann MF: Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat Immunol 2002, 8: 373-378. 10.1038\/nm0402-373","journal-title":"Nat Immunol"},{"key":"775_CR20","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.4049\/jimmunol.173.4.2524","volume":"173","author":"AH Kim","year":"2004","unstructured":"Kim AH, Dimitriou ID, Holland MC, Mastellos D, Mueller YM, Altman JD, Lambris JD, Katsikis PD: Complement C5a receptor is essential for the optimal generation of antiviral CD8 + T cell responses. J Immunol 2004, 173: 2524-2529.","journal-title":"J Immunol"},{"key":"775_CR21","doi-asserted-by":"crossref","first-page":"6410","DOI":"10.4049\/jimmunol.151.11.6410","volume":"151","author":"M Mulligan","year":"1993","unstructured":"Mulligan M, Watson S, Fennie C, Ward P: Protective effects of selectin chimeras in neutrophil-mediated lung injury. J Immunol 1993, 151: 6410-6417.","journal-title":"J Immunol"},{"key":"775_CR22","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nm0402-373","volume":"8","author":"M Kopf","year":"2002","unstructured":"Kopf M, Abel B, Gallimore A, Carroll M, Bachmann MF: Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat Med 2002, 8: 373-378. 10.1038\/nm0402-373","journal-title":"Nat Med"},{"key":"775_CR23","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1084\/jem.186.2.199","volume":"186","author":"U Martin","year":"1997","unstructured":"Martin U, Bock D, Arseniev L, Tornetta MA, Ames RS, Bautsch W, K\u00f6hl J, Ganser A, Klos A: The human C3a receptor is expressed on neutrophils and monocytes, but not on Bor Tlymphocytes. J Exp Med 1997, 186: 199-207. 10.1084\/jem.186.2.199","journal-title":"J Exp Med"},{"key":"775_CR24","first-page":"6","volume":"24","author":"U Hohenthal","year":"2006","unstructured":"Hohenthal U, Nuutila J, Lilius EM, Laitinen I, Nikoskelainen J, Kotilainen P: Measurement of complement receptor 1 on neutrophils in bacterial and viral pneumonia. BMC Infect Dis 2006, 24: 6-11.","journal-title":"BMC Infect Dis"},{"key":"775_CR25","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.jim.2006.07.021","volume":"315","author":"J Nuutila","year":"2006","unstructured":"Nuutila J, Hohenthal U, Laitinen I, Kotilainen P, Rajam\u00e4ki A, Nikoskelainen J, Lilius EM: Quantitative analysis of complement receptors, CR1 (CD35) and CR3 (CD11b), on neutrophils improves distinction between bacterial and viral infections in febrile patients: comparison with standard clinical laboratory data. J Immunol Methods 2006, 315: 191-201. 10.1016\/j.jim.2006.07.021","journal-title":"J Immunol Methods"},{"key":"775_CR26","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1046\/j.1365-2567.1999.00781.x","volume":"97","author":"T Kase","year":"1999","unstructured":"Kase T, Suzuki Y, Kawai T, Sakamoto T, Ohtani K, Eda S, Maeda A, Okuno Y, Kurimura T, Wakamiya N: Human mannan-binding lectin inhibits the infection of influenza A virus without complement. Immunology 1999, 97: 385-392. 10.1046\/j.1365-2567.1999.00781.x","journal-title":"Immunology"},{"key":"775_CR27","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/77802","volume":"1","author":"TM Ross","year":"2000","unstructured":"Ross TM, Xu Y, Bright RA, Robinson HL: C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge. Nat Immunol 2000, 1: 127-131. 10.1038\/77802","journal-title":"Nat Immunol"},{"key":"775_CR28","doi-asserted-by":"publisher","first-page":"4532","DOI":"10.1016\/S0264-410X(03)00510-3","volume":"21","author":"I Watanabe","year":"2003","unstructured":"Watanabe I, Ross TM, Tamura S, Ichinohe T, Ito S, Takahashi H, Sawa H, Chiba J, Kurata T, Sata T, Hasegawa H: Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin. Vaccine 2003, 21: 4532-4538. 10.1016\/S0264-410X(03)00510-3","journal-title":"Vaccine"},{"key":"775_CR29","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1002\/eji.200636755","volume":"37","author":"MP Longhi","year":"2007","unstructured":"Longhi MP, Williams A, Matthew Wise, Paul Morgan B, Gallimore Awen: CD59a deficiency exacerbates influenza-induced lung inflammation through complement-dependent and-independent mechanisms. Eur J Immunol 2007, 37: 1266-1274. 10.1002\/eji.200636755","journal-title":"Eur J Immunol"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1743-422X-7-30.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T04:43:52Z","timestamp":1685421832000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/1743-422X-7-30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2,9]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["775"],"URL":"https:\/\/doi.org\/10.1186\/1743-422x-7-30","relation":{},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,2,9]]},"assertion":[{"value":"14 January 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"30"}}