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甲型流感病毒是人类最重要的病原体之一，可导致大量季节性和大流行性感染，尤其是儿童流行感染，进而引发较高的发病率和死亡率。甲型流感病毒感染引起的呼吸道感染性疾病具有极高的传染性、发病率及病死率，其感染机制较为复杂，尚未得到全面阐述。本文总结了甲型流感病毒感染过程中在分子水平上病毒与宿主相互作用，并重点阐述了一些关键的细胞反应。本文还讨论了免疫介导的甲型流感病毒清除机制、促进免疫反应或引起肺损伤的机制、流感病毒诱导损伤后的肺部再生过程，以及预防流感最新研究进展，为后续研究提供相关思路及理论指导，以期为流感病毒引起的疾病带来新的有效诊疗方法。
Abstract：Influenza A virus(IAV) is one of the most significant human pathogens, responsible for both seasonal epidemics and global pandemics. It poses a particular threat to children and is associated with high morbidity and mortality. Respiratory infections caused by IAV are highly contagious and often lead to severe pulmonary complications. Despite extensive research, the pathogenic mechanisms underlying IAV infection remain incompletely understood. This review summarizes the molecular-level interactions between IAV and host cells during infection, with a focus on key cellular responses. It further explores immune-mediated viral clearance mechanisms, as well as immune responses that contribute to lung injury. The process of lung regeneration following IAV-induced damage is also discussed. In addition, the review highlights recent advances in influenza prevention strategies. Together, these insights provide a foundation for future studies and may contribute to the development of novel and effective therapeutic approaches for IAV-induced diseases.
[1]白红岩，李希妍，黄维娟，等.甲型H3N2亚型流感病毒重配疫苗株产量评估与基因特性研究[J].病毒学报，2024, 40(06):1246-1254. DOI:10. 13242/j. cnki.bingduxuebao. 004618.
[2]Ortiz JR, Neuzil KM, Rue TC, et al. Population-based incidence estimates of influenza-associated respiratory failure hospitalizations, 2003 to 2009[J]. Am J Respir Crit Care Med, 2013, 188(6):710-715. DOI:10. 1164/rccm. 201212-2341OC.
[3]Pisesky A, Benchimol EI, Wong CA, et al. Incidence of hospitalization for respiratory syncytial virus infection amongst children in Ontario, Canada:a populationbased study using validated health administrative data[J]. PLoS One, 2016, 11(3):e0150416. DOI:10. 1371/journal. pone. 0150416.
[4]Thampi N, Knight BD, Thavorn K, et al. Health care costs of hospitalization of young children for respiratory syncytial virus infections:a population-based matched cohort study[J]. CMAJ Open, 2021, 9(4):E948-E956. DOI:10. 9778/cmajo. 20200219.
[5]Blanken MO, Rovers MM, Molenaar JM, et al.Respiratory syncytial virus and recurrent wheeze in healthy preterm infants[J]. N Engl J Med, 2013, 368(19):1791-1799. DOI:10. 1056/NEJMoa1211917.
[6]Binns E, Tuckerman J, Licciardi PV, et al. Respiratory syncytial virus, recurrent wheeze and asthma:a narrative review of pathophysiology, prevention and future directions[J]. J Paediatr Child Health, 2022, 58(10):1741-1746. DOI:10. 1111/jpc. 16197.
[7]Hoover J, Eades S, Lam WM. Pediatric antiviral stewardship:defining the potential role of ribavirin in respiratory syncytial virus-associated lower respiratory illness[J]. J Pediatr Pharmacol Ther, 2018, 23(5):372-378. DOI:10. 5863/1551-6776-23. 5. 372.
[8]Sinclair SM, Jones JK, Miller RK, et al. The ribavirin pregnancy registry:an interim analysis of potential teratogenicity at the mid-point of enrollment[J]. Drug Saf, 2017, 40(12):1205-1218. DOI:10. 1007/s40264-017-0566-6.
[9]Alansari K, Toaimah FH, Almatar DH, et al.Monoclonal antibody treatment of RSV bronchiolitis in young infants:a randomized trial[J]. Pediatrics, 2019,143(3):e20182308. DOI:10. 1542/peds. 2018-2308.
[10]Sáez-Llorens X, Moreno MT, Ramilo O, et al. Safety and pharmacokinetics of palivizumab therapy in children hospitalized with respiratory syncytial virus infection[J].Pediatr Infect Dis J, 2004, 23(8):707-712. DOI:10. 1097/01. inf. 0000133165. 85909. 08.
[11]Ramilo O, Lagos R, Sáez-Llorens X, et al.Motavizumab treatment of infants hospitalized with respiratory syncytial virus infection does not decrease viral load or severity of illness[J]. Pediatr Infect Dis J,2014, 33(7):703-709. DOI:10. 1097/INF. 0000000000000240.
[12]Sanders SL, Agwan S, Hassan M, et al.Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection[J]. Cochrane Database Syst Rev, 2019, 8(8):CD009417. DOI:10. 1002/14651858. CD009417.pub2.
[13]王传宝，季圣翔，李成伟，等.学校流感暴发疫情环境病毒感染特征分析[J].病毒学报，2024, 40(6):1378-1383. DOI:10. 13242/j. cnki. bingduxuebao. 004579.
[14]Mohapatra SS, Boyapalle S. Epidemiologic,experimental, and clinical links between respiratory syncytial virus infection and asthma[J]. Clin Microbiol Rev, 2008, 21(3):495-504. DOI:10. 1128/CMR. 00054-07.
[15]Larkin EK, Hartert TV. Genes associated with RSV lower respiratory tract infection and asthma:the application of genetic epidemiological methods to understand causality[J]. Future Virol, 2015, 10(7):883-897. DOI:10. 2217/fvl. 15. 55.
[16]Linssen RN, Ma J, Bem RA, et al. Rational use of mucoactive medications to treat pediatric airway disease[J]. Paediatr Respir Rev, 2020, 36:8-14. DOI:10. 1016/j. prrv. 2020. 06. 007.
[17]Faber TE, Kamps AW, Sjoerdsma MH, et al.Computerized assessment of wheezing in children with respiratory syncytial virus bronchiolitis before and after hypertonic saline nebulization[J]. Respir Care, 2015, 60(9):1252-1256. DOI:10. 4187/respcare. 03754.
[18]Morikawa Y, Miura M, Furuhata MY, et al. Nebulized hypertonic saline in infants hospitalized with moderately severe bronchiolitis due to RSV infection:a multicenter randomized controlled trial[J]. Pediatr Pulmonol,2018, 53(3):358-365. DOI:10. 1002/ppul. 23945.
[19]Naz F, Raza AB, Ijaz I, et al. Effectiveness of nebulized N-acetylcysteine solution in children with acute bronchiolitis[J]. J Coll Physicians Surg Pak, 2014, 24(6):408-411.
[20]Jaquet-Pilloud R, Verga ME, Russo M, et al.Nebulised hypertonic saline in moderate-to-severe bronchiolitis:a randomised clinical trial[J]. Arch Dis Child, 2020, 105(3):236-240. DOI:10. 1136/archdischild-2019-317160.
[21]Rodríguez-Martínez CE, Nino G, Castro-Rodriguez JA, et al. For which infants with viral bronchiolitis could it be deemed appropriate to use albuterol, at least on a therapeutic trial basis?[J]. Allergol Immunopathol(Madr), 2021, 49(1):153-158. DOI:10. 15586/aei.v49i1. 12.
[22]李珊，董卉，姚雪，等. H10N3禽流感病毒安徽分离株遗传多样性研究[J].病毒学报，2024, 40(05):1022-1032. DOI:10. 13242/j. cnki. bingduxuebao. 004578.
[23]Everard ML, Swarbrick A, Wrightham M, et al.Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection[J]. Arch Dis Child, 1994, 71(5):428-432. DOI:10. 1136/adc. 71. 5. 428.
[24]Alansari K, Sakran M, Davidson BL, et al. Oral dexamethasone for bronchiolitis:a randomized trial[J].Pediatrics, 2013, 132(4):e810-6. DOI:10. 1542/peds. 2012-3746.
[25]Pinto LA, Pitrez PM, Luisi F, et al. Azithromycin therapy in hospitalized infants with acute bronchiolitis is not associated with better clinical outcomes:a randomized, double-blinded, and placebo-controlled clinical trial[J]. J Pediatr, 2012, 161(6):1104-1108.DOI:10. 1016/j. jpeds. 2012. 05. 053.
[26]Tal G, Cesar K, Oron A, et al. Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchiolitis reduces hospitalization stay:2 years experience[J]. Isr Med Assoc J, 2006, 8(3):169-173.
[27]Carlos Flores-González J, Matamala-Morillo MA,Rodríguez-Campoy P, et al. Epinephrine improves the efficacy of nebulized hypertonic saline in moderate bronchiolitis:a randomised clinical trial[J]. PLoS One,2015, 10(11):e0142847. DOI:10. 1371/journal.pone. 0142847.
[28]Goldbart A, Lavie M, Lubetzky R, et al. Inhaled nitric oxide for the treatment of acute bronchiolitis:a multicenter randomized controlled clinical trial to evaluate dose response[J]. Ann Am Thorac Soc,2023, 20(2):236-244. DOI:10. 1513/AnnalsATS. 202103-348OC.
[29]Hasegawa K, Dumas O, Hartert TV, et al. Advancing our understanding of infant bronchiolitis through phenotyping and endotyping:clinical and molecular approaches[J]. Expert Rev Respir Med, 2016, 10(8):891-899. DOI:10. 1080/17476348. 2016. 1190647.
[30]Kutsaya A, Teros-Jaakkola T, Kakkola L, et al.Prospective clinical and serological follow-up in early childhood reveals a high rate of subclinical RSV infection and a relatively high reinfection rate within the first 3years of life[J]. Epidemiol Infect, 2016, 144(8):1622-1633. DOI:10. 1017/S0950268815003143.
[31]Bont L, Versteegh J, Swelsen WTN, et al. Natural reinfection with respiratory syncytial virus does not boost virus-specific T-cell immunity[J]. Pediatr Res, 2002,52(3):363-367. DOI:10. 1203/00006450-200209000-00009.
[32]Mazur NI, Terstappen J, Baral R, et al. Respiratory syncytial virus prevention within reach:the vaccine and monoclonal antibody landscape[J]. Lancet Infect Dis,2023, 23(1):e2-e21. DOI:10. 1016/S1473-3099(22)00291-2.
[33]Mazur NI, Higgins D, Nunes MC, et al. The respiratory syncytial virus vaccine landscape:lessons from the graveyard and promising candidates[J]. Lancet Infect Dis, 2018, 18(10):e295-e311. DOI:10. 1016/S1473-3099(18)30292-5.
[34]Mejias A, Rodríguez-Fernández R, Oliva S, et al. The journey to a respiratory syncytial virus vaccine[J]. Ann Allergy Asthma Immunol, 2020, 125(1):36-46. DOI:10. 1016/j. anai. 2020. 03. 017.
[35]McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer bound to a prefusionspecific neutralizing antibody[J]. Science, 2013, 340(6136):1113-1117. DOI:10. 1126/science. 1234914.
[36]Krarup A, Truan D, Furmanova-Hollenstein P, et al.A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism[J]. Nat Commun, 2015, 6:8143. DOI:10. 1038/ncomms9143.
[37]Madhi SA, Polack FP, Piedra PA, et al. Respiratory syncytial virus vaccination during pregnancy and effects in infants[J]. N Engl J Med, 2020, 383(5):426-439.DOI:10. 1056/NEJMoa1908380.
[38]Falsey AR, Sobieszczyk ME, Hirsch I, et al. Phase 3safety and efficacy of AZD1222(ChAdOx1 nCoV-19)covid-19 vaccine[J]. N Engl J Med, 2021, 385(25):2348-2360. DOI:10. 1056/NEJMoa2105290.
[39]Kanack AJ, Padmanabhan A. Vaccine-induced immune thrombotic thrombocytopenia[J]. Best Pract Res Clin Haematol, 2022, 35(3):101381. DOI:10. 1016/j.beha. 2022. 101381.
[40]Aliprantis AO, Shaw CA, Griffin P, et al. A phase 1,randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults[J]. Hum Vaccin Immunother, 2021, 17(5):1248-1261. DOI:10. 1080/21645515. 2020. 1829899.
[41]Crank MC, Ruckwardt TJ, Chen M, et al. A proof of concept for structure-based vaccine design targeting RSV in humans[J]. Science, 2019, 365(6452):505-509. DOI:10. 1126/science. aav9033.
[42]Korteweg C, Gu J. Pathology, molecular biology, and pathogenesis of avian influenza A(H5N1)infection in humans[J]. Am J Pathol, 2008, 172(5):1155-1170.DOI:10. 2353/ajpath. 2008. 070791.
[43]Karron RA, Atwell JE, McFarland EJ, et al. Liveattenuated vaccines prevent respiratory syncytial virusassociated illness in young children[J]. Am J Respir Crit Care Med, 2021, 203(5):594-603. DOI:10. 1164/rccm. 202005-1660OC.
[44]Abarca K, Rey-Jurado E, Mu?oz-Durango N, et al.Safety and immunogenicity evaluation of recombinant BCG vaccine against respiratory syncytial virus in a randomized, double-blind, placebo-controlled phase I clinical trial[J]. EClinicalMedicine, 2020, 27:100517.DOI:10. 1016/j. eclinm. 2020. 100517.
[45]American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection[J]. Pediatrics, 2014, 134(2):e620-38. DOI:10. 1542/peds. 2014-1666.
[46]Garegnani L, Styrmisdóttir L, Roson Rodriguez P, et al. Palivizumab for preventing severe respiratory syncytial virus(RSV)infection in children[J].Cochrane Database Syst Rev, 2021, 11(11):CD013757. DOI:10. 1002/14651858. CD013757.pub2.
[47]Ananworanich J, Heaton PM. Bringing preventive RSV monoclonal antibodies to infants in low-and middleincome countries:challenges and opportunities[J].Vaccines(Basel), 2021, 9(9):961. DOI:10. 3390/vaccines9090961.
[48]Feltes TF, Sondheimer HM, Tulloh RMR, et al. A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease[J]. Pediatr Res,2011, 70(2):186-191. DOI:10. 1203/PDR. 0b013e318220a553.
[49]Venkatesan P. Nirsevimab:a promising therapy for RSV[J]. Lancet Microbe, 2022, 3(5):e335. DOI:10. 1016/S2666-5247(22)00097-0.
[50]Brandes M, Klauschen F, Kuchen S, et al. A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection[J]. Cell, 2013, 154(1):197-212. DOI:10. 1016/j. cell. 2013. 06. 013.
[51]Morens DM, Taubenberger JK, Fauci AS.Predominant role of bacterial pneumonia as a cause of death in pandemic influenza:implications for pandemic influenza preparedness[J]. J Infect Dis, 2008, 198(7):962-970. DOI:10. 1086/591708.
[52]Guo H, Topham DJ. Interleukin-22(IL-22)production by pulmonary Natural Killer cells and the potential role of IL-22 during primary influenza virus infection[J]. J Virol, 2010, 84(15):7750-7759. DOI:10. 1128/JVI. 00187-10.
[53]Aujla SJ, Chan YR, Zheng M, et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia[J]. Nat Med, 2008, 14(3):275-281. DOI:10. 1038/nm1710.
[54]Mrowczynski OD, Zacharia BE, Connor JR. Exosomes and their implications in central nervous system tumor biology[J]. Prog Neurobiol, 2019, 172:71-83. DOI:10. 1016/j. pneurobio. 2018. 06. 006.
[55]Miura TA. Respiratory epithelial cells as master communicators during viral infections[J]. Curr Clin Microbiol Rep, 2019, 6(1):10-17. DOI:10. 1007/s40588-019-0111-8.
[56]Narasaraju T, Ng HH, Phoon MC, et al. MCP-1antibody treatment enhances damage and impedes repair of the alveolar epithelium in influenza pneumonitis[J].Am J Respir Cell Mol Biol, 2010, 42(6):732-743.DOI:10. 1165/rcmb. 2008-0423OC.
[57]Anikina AG, Shkurupii VA, Potapova OV, et al.Expression of profibrotic growth factors and their receptors by mouse lung macrophages and fibroblasts under conditions of acute viral inflammation in influenza A/H5N1 virus[J]. Bull Exp Biol Med, 2014, 156(6):833-837. DOI:10. 1007/s10517-014-2463-7.
[58]Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccination of pregnant women and protection of their infants[J]. N Engl J Med, 2014, 371(10):918-931.DOI:10. 1056/NEJMoa1401480.
[59]Shirey KA, Lai W, Scott AJ, et al. The TLR4antagonist Eritoran protects mice from lethal influenza infection[J]. Nature, 2013, 497(7450):498-502.DOI:10. 1038/nature12118.
[60]Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure[J].Nature, 2005, 436(7047):112-116. DOI:10. 1038/nature03712.
[61]Karlstr?m A, Boyd KL, Keith English B, et al.Treatment with protein synthesis inhibitors improves outcomes of secondary bacterial pneumonia after influenza[J]. J Infect Dis, 2009, 199(3):311-319.DOI:10. 1086/596051.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250118
中图分类号:R511.7
引用信息:
[1]税丹,杜永丽,罗妤菲,等.甲型流感病毒诱发的肺损伤致病机制及预防措施研究进展[J].病毒学报,2025,41(05):1573-1580.DOI:10.13242/j.cnki.bingduxuebao.250118.
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