目的: 研究人腺病毒（human adenovirus,HAdV）感染后呼吸道上皮细胞中的λ1干扰素（interferon-λ1,IFN-λ1）的表达情况。方法: 选取2019年1―12月因腺病毒肺炎住院的143例患儿为HAdV组,另选取同期35例呼吸道病原结果均阴性者作对照组,采集鼻咽拭子提取核酸,用荧光定量 PCR 检测病毒载量、IFN-λ1 mRNA 表达水平和HAdV测序分型。结果: HAdV组、HAdV组中不同年龄段、单纯感染组、混合感染组、重症组、非重症组、HAdV-3组、HAdV-7 组IFN-λ1 mRNA的表达水平均低于对照组。重症组HAdV载量高于非重症组;HAdV组、重症组、HAdV-7组的IFN-λ1 mRNA的表达水平与病毒载量有相关性。结论: 儿童腺病毒肺炎病情严重程度与病毒载量相关,其IFN-λ1表达水平降低,提示IFN-λ1可能参与了腺病毒感染的疾病进程。
Abstract
Objective To study the expression of IFN-λ1 in respiratory epithelial cells infected with human adenovirus (HAdV). Methods 143 children hospitalized with adenovirus pneumonia from January to December, 2019 were selected as the HAdV group, and 35 patients with negative sputum culture and seven respiratory antigens were selected as the control group. Nasopharyngeal swabs were collected to extract nucleic acids, and the viral load, IFN-λ1mRNA expression level and HAdV sequencing typing were detected by fluorescence quantitative PCR. Results The expression levels of IFN-λ1mRNA in HAdV group and HAdV group at different ages, simple infection group, mixed infection group, severe group, non-severe group, HAdV-3 group and HAdV-7 group were lower than those in the control group (P<0.05). The HAdV load in severe group was higher than that in non-severe group (P<0.05). The expression level of IFN-λ1mRNA in HAdV group, severe group and HAdV-7 group was correlated with viral load (P<0.01). Conclusion The severity of adenovirus pneumonia in children is related to the viral load but not to the expression of IFN-λ1, and the expression level of IFN-λ1 is decreased, suggesting that IFN-λ1 may be involved in the disease process of adenovirus infection.
关键词
儿童 /
腺病毒肺炎 /
干扰素-λ1
Key words
children /
adenovirus pneumonia /
interferon-λ1
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参考文献
[1] XIE L, ZHANG B, ZHOU J, et al.Human adenovirus load in respiratory tract secretions are predictors for disease severity in children with human adenovirus pneumonia[J]. Virol J, 2018, 15(1): 123.
[2] SUN Q, JIANG W, CHEN Z, et al.Epidemiology and clinical features of respiratory adenoviral infections in children[J]. Eur J Pediatr, 2014, 173(4) : 441-444.
[3] LION T.Adenovirus Infections in Immunocompetent and Immunocompromised Patients[J]. Clinical Microbiology Reviews,2014,27(3):441-462.
[4] ANDREAKOS E, ZANONI I, GALANI I E.Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control[J]. Curr Opin Immunol, 2019, 56: 67-75.
[5] KOTENKO S V, DURBIN J E.Contribution of type III interferons to antiviral immunity: location, location, location[J]. J biol chem, 2017, 292(18) : 7295-7303.
[6] HOLLY M K, SMITH J G, PFEIFFER J K.Adenovirus Infection of Human Enteroids Reveals Interferon Sensitivity and Preferential Infection of Goblet Cells[J]. J virol, 2018, 92(9): e00250-18 .
[7] SHERWOOD V, KING E, TÖTEMEYER S, et al. Interferon treatment suppresses enteric adenovirus infection in a model gastrointestinal cell-culture system[J]. J Gen Virol, 2012, 93(3) : 618-623.
[8] ZHENG Y, STAMMINGER T, HEARING P.E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection[J]. PLOS Pathogens, 2016, 12(1) : 1-24.
[9] 倪鑫. 儿童腺病毒肺炎诊疗规范 (2019年版)[J]. 全科医学临床与教育, 2019, 17(7) : 579-583.
[10] 倪鑫. 儿童社区获得性肺炎诊疗规范 (2019年版)[J]. 全科医学临床与教育, 2019, 17(9) : 771-777.
[11] SUGIYAMA M, KIMURA T, NAITO S, et al.Development of specific and quantitative real-time detection PCR and immunoassays for λ3-interferon[J]. Hepatol Res, 2012, 42(11) : 1089-1099.
[12] SELVAGGI C, PIERANGELI A, FABIANI M, et al.Interferon lambda 1-3 expression in infants hospitalized for RSV or HRV associated bronchiolitis[J]. J Infect, 2014, 68(5) : 467-477.
[13] SHEPPARD P, KINDSVOGEL W, XU W, et al.IL-28, IL-29 and their class II cytokine receptor IL-28R[J]. Nat Immunol, 2003, 4(1) : 63-68.
[14] KLINKHAMMER J, SCHNEPF D, YE L, et al.IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission[J]. eLife, 2018, 7: e33354.
[15] BROGGI A, GRANUCCI F, ZANONI I.Type III interferons: Balancing tissue tolerance and resistance to pathogen invasion[J]. J Exp Med, 2020, 217(1): e20190295.
[16] FU Y, TANG Z, YE Z, et al.Human adenovirus type 7 infection causes a more severe disease than type 3[J]. BMC Infect Dis, 2019, 19(1) : 36.
[17] 陶美婷, 谢亚平, 刘淑萍, 等. RSV感染患儿呼吸道上皮细胞中干扰素-λ1的表达水平及其与RSV载量的关系[J]. 中国当代儿科杂志, 2017, 19(06) : 677-681.
[18] 林小娟, 钟礼立, 谢亚平, 等. 干扰素-λ1在人类鼻病毒感染后儿童呼吸道上皮细胞中的表达[J]. 中国当代儿科杂志, 2019, 21(12) : 1177-1181.
[19] 杨焯杰, 彭力, 钟礼立, 等. 流感病毒感染后儿童呼吸道上皮细胞中干扰素-λ1表达水平的临床研究[J]. 湖南师范大学学报 (医学版), 2022, 19(02) : 15-19.
[20] Trinchieri G.Type I interferon: friend or foe?[J]. J Exp Med, 2010, 207(10) : 2053-2063.
[21] CHAHAL J S, GALLAGHER C, DEHART C J, et al.The Repression Domain of the E1B 55-Kilodalton Protein Participates in Countering Interferon-Induced Inhibition of Adenovirus Replication[J]. J Virol, 2013, 87(8) : 4432-4444.
[22] 廖蔻, 代继宏, 钟林平, 等. 基于决策曲线和剂量反应分析评估腺病毒载量对儿童感染重症腺病毒肺炎后发展为闭塞性细支气管炎的预测价值[J]. 中国循证儿科杂志, 2019, 14(5) : 342-346.
[23] MAJOR J, CROTTA S, LLORIAN M, et al.Type I and III interferons disrupt lung epithelial repair during recovery from viral infection[J]. Science, 2020, 369(6504) : 712-717.
基金
湖南省创新型省份建设专项（2020JJ8011）
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