流感病毒研究进展

doi:10.3969/j.issn.1673-8640.2023.07.015

摘要/Abstract

摘要：

流行性感冒（简称流感）是由流感病毒感染所致的具有高度传染性的急性呼吸道疾病，具有强致病性和高病死率。近年来，针对流感病毒的研究已取得了一定的进展，但流感病毒的药物和疫苗研发仍存在不足。目前，对于流感病毒的发展趋势和病毒变异情况尚无法预测，仍需广大科研工作者对流感病毒的病原学和致病机制进行深入研究。文章就流感病毒的病原学、流行病学、致病机制、流感相关性肺炎和急性呼吸窘迫综合征、药物研发等进行综述。

关键词: 流感病毒, 流行病学, 宿主免疫反应, 细胞凋亡, 流感相关性肺炎, 急性呼吸窘迫综合征

Abstract:

Influenza is a highly infectious acute respiratory disease caused by influenza virus infection. It has severe pathogenicity and high mortality. In the recent years，the study of influenza viruses has made certain progress，but in the development of drugs and vaccines for influenza viruses it is still inadequate，and the development trend of influenza virus variation situation at present can not be predicted，so this needs scientific research workers focusing on the etiology and pathogenic mechanism of influenza viruses. In this review，the etiology，epidemiology，pathogenic mechanism，influenza-associated pneumonia and acute respiratory distress syndrome were reviewed.

Key words: Influenza virus, Epidemiology, Host immune response, Cell apoptosis, Influenza-associated pneumonia, Acute respiratory distress syndrome

中图分类号:

R373.1

陈丹阳, 郑思钰, 郑锐林, 苏静瑶, 朱冰, 李英华. 流感病毒研究进展[J]. 检验医学, 2023, 38(7): 696-703.

CHEN Danyang, ZHENG Siyu, ZHENG Ruilin, SU Jingyao, ZHU Bing, LI Yinghua. Research progress in influenza viruses[J]. Laboratory Medicine, 2023, 38(7): 696-703.

图/表 1

参考文献 47

[1]	KALIL A C, THOMAS P G. Influenza virus-related critical illness:pathophysiology and epidemiology[J]. Crit Care, 2019, 23(1):258. DOI
[2]	CHAISRI U, CHAICUMPA W. Evolution of therapeutic antibodies,influenza virus biology,influenza,and influenza immunotherapy[J]. Biomed Res Int, 2018, 2018:9747549.
[3]	SHAHAM A, CHODICK G, SHALEV V, et al. Personal and social patterns predict influenza vaccination decision[J]. BMC Public Health, 2020, 20(1):222. DOI PMID
[4]	BAILEY E S, CHOI J Y, FIELDHOUSE J K, et al. The continual threat of influenza virus infections at the human-animal interface:what is new from a one health perspective?[J]. Evol Med Public Health, 2018, 2018(1):192-198. DOI URL
[5]	KRAMMER F, SMITH G J D, FOUCHIER R A M, et al. Influenza[J]. Nat Rev Dis Primers, 2018, 4(1):3. DOI PMID
[6]	SAUNDERS-HASTINGS P R, KREWSKI D. Reviewing the history of pandemic influenza:understanding patterns of emergence and transmission[J]. Pathogens, 2016, 5(4):66. DOI URL
[7]	TRAN D, VAUDRY W, MOORE D, et al. Hospitalization for influenza A versus B[J]. Pediatrics, 2016, 138(3):e20154643. DOI URL
[8]	FLERLAGE T, BOYD D F, MELIOPOULOS V, et al. Influenza virus and SARS-CoV-2:pathogenesis and host responses in the respiratory tract[J]. Nat Rev Microbiol, 2021, 19(7):425-441. DOI
[9]	LAZNIEWSKI M, DAWSON W K, SZCZEPINSKA T, et al. The structural variability of the influenza A hemagglutinin receptor-binding site[J]. Brief Funct Genomics, 2018, 17(6):415-427. DOI PMID
[10]	DU W, DE VRIES E, VAN KUPPEVELD F J M, et al. Second sialic acid-binding site of influenza A virus neuraminidase:binding receptors for efficient release[J]. FEBS J, 2021, 288(19):5598-5612. DOI URL
[11]	TAVARES L P, TEIXEIRA M M, GARCIA C C. The inflammatory response triggered by influenza virus:a two edged sword[J]. Inflamm Res, 2017, 66(4):283-302. DOI
[12]	RAMOS I, FERNANDEZ-SESMA A. Modulating the innate immune response to influenza A virus:potential therapeutic use of anti-inflammatory drugs[J]. Front Immunol, 2015, 6:361.
[13]	BOWIE A G, UNTERHOLZNER L. Viral evasion and subversion of pattern-recognition receptor signalling[J]. Nat Rev Immunol, 2008, 8(12):911-922. DOI PMID
[14]	DUAN M, HIBBS M L, CHEN W. The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis[J]. Immunol Cell Biol, 2017, 95(3):225-235. DOI PMID
[15]	KOSTADINOVA E, CHAPUT C, GUTBIER B, et al. NLRP3 protects alveolar barrier integrity by an inflammasome-independent increase of epithelial cell adherence[J]. Sci Rep, 2016, 6:30943. DOI PMID
[16]	TAN K S, LIM R L, LIU J, et al. Respiratory viral infections in exacerbation of chronic airway inflammatory diseases:novel mechanisms and insights from the upper airway epithelium[J]. Front Cell Dev Biol, 2020, 8:99. DOI URL
[17]	LAMICHHANE P P, SAMARASINGHE A E. The role of innate leukocytes during influenza virus infection[J]. J Immunol Res, 2019, 2019:8028725.
[18]	LI K, MCCAW J M, CAO P. Modelling within-host macrophage dynamics in influenza virus infection[J]. J Theor Biol, 2021, 508:110492. DOI URL
[19]	HÖGNER K, WOLFF T, PLESCHKA S, et al. Correction:macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia[J]. PLoS Pathog, 2016, 12(6):e1005716. DOI URL
[20]	WANG X, SUN Q, YE Z, et al. Computational approach for predicting the conserved B-cell epitopes of hemagglutinin H7 subtype influenza virus[J]. Exp Ther Med, 2016, 12(4):2439-2446. PMID
[21]	AMPOMAH P B, LIM L H K. Influenza A virus-induced apoptosis and virus propagation[J]. Apoptosis, 2020, 25(1-2):1-11. DOI PMID
[22]	ATKIN-SMITH G K, DUAN M, CHEN W, et al. The induction and consequences of influenza A virus-induced cell death[J]. Cell Death Dis, 2018, 9(10):1002. DOI
[23]	WANG R, ZHU Y, REN C, et al. Influenza A virus protein PB1-F2 impairs innate immunity by inducing mitophagy[J]. Autophagy, 2021, 17(2):496-511. DOI URL
[24]	MAYANK A K, SHARMA S, NAILWAL H, et al. Nucleoprotein of influenza A virus negatively impacts antiapoptotic protein API5 to enhance E2F1-dependent apoptosis and virus replication[J]. Cell Death Dis, 2015, 6(12): e2018.
[25]	EL-SAYED I, BASSIOUNY K, NOKALY A, et al. Influenza A virus and influenza B virus can induce apoptosis via intrinsic or extrinsic pathways and also via NF-κB in a time and dose dependent manner[J]. Biochem Res Int, 2016, 2016:1738237.
[26]	WANG X, TAN J, ZOUEVA O, et al. Novel pandemic influenza A(H1N1)virus infection modulates apoptotic pathways that impact its replication in A549 cells[J]. Microbes Infect, 2014, 16(3):178-186. DOI URL
[27]	LAM W Y, TANG J W, YEUNG A C, et al. Avian influenza virus A/HK/483/97(H5N1)NS1 protein induces apoptosis in human airway epithelial cells[J]. J Virol, 2008, 82(6):2741-2751. DOI URL
[28]	ZHANG T, YIN C, BOYD D F, et al. Influenza virus Z-RNAs induce ZBP1-mediated necroptosis[J]. Cell, 2020, 180(6):1115-1129. DOI PMID
[29]	LAGHLALI G, LAWLOR K E, TATE M D. Die another way:interplay between influenza a virus,inflammation and cell death[J]. Viruses, 2020, 12(4):401. DOI URL
[30]	BALACHANDRAN S, RALL G F. Benefits and perils of necroptosis in influenza virus infection[J]. J Virol, 2020, 94(9):e01101- e01119.
[31]	NOGUSA S, THAPA R J, DILLON C P, et al. RIPK3 activates parallel pathways of MLKL-driven necroptosis and FADD-mediated apoptosis to protect against influenza A virus[J]. Cell Host Microbe, 2016, 20(1):13-24. DOI PMID
[32]	YATIM N, CULLEN S, ALBERT M L. Dying cells actively regulate adaptive immune responses[J]. Nat Rev Immunol, 2017, 17(4):262-275. DOI PMID
[33]	GABA A, XU F, LU Y, et al. The NS1 protein of influenza A virus participates in necroptosis by interacting with MLKL and increasing its oligomerization and membrane translocation[J]. J Virol, 2019, 93(2):e01835-18.
[34]	HEO J Y, SONG J Y, NOH J Y, et al. Effects of influenza immunization on pneumonia in the elderly[J]. Hum Vaccin Immunother, 2018, 14(3):744-749. DOI URL
[35]	METERSKY M L, MASTERTON R G, LODE H, et al. Epidemiology,microbiology,and treatment considerations for bacterial pneumonia complicating influenza[J]. Int J Infect Dis, 2012, 16(5):e321-e331.
[36]	WYPYCH T P, WICKRAMASINGHE L C, MARSLAND B J. The influence of the microbiome on respiratory health[J]. Nat Immunol, 2019, 20(10):1279-1290. DOI PMID
[37]	METZGER D W, SUN K. Immune dysfunction and bacterial coinfections following influenza[J]. J Immunol, 2013, 191(5):2047-2052. DOI PMID
[38]	BAL A, CASALEGNO J S, MELENOTTE C, et al. Influenza-induced acute respiratory distress syndrome during the 2010-2016 seasons:bacterial co-infections and outcomes by virus type and subtype[J]. Clin Microbiol Infect, 2020, 26(7):947.e1-947.e4.
[39]	XU J, YU J, YANG L, et al. Influenza virus in community-acquired pneumonia:current understanding and knowledge gaps[J]. Semin Respir Crit Care Med, 2020, 41(4):555-567. DOI URL
[40]	BRAND J D, LAZRAK A, TROMBLEY J E, et al. Influenza-mediated reduction of lung epithelial ion channel activity leads to dysregulated pulmonary fluid homeostasis[J]. JCI Insight, 2018, 3(20):e123467. DOI URL
[41]	GUO X J, THOMAS P G. New fronts emerge in the influenza cytokine storm[J]. Semin Immunopathol, 2017, 39(5):541-550. DOI
[42]	SHIE J J, FANG J M. Development of effective anti-influenza drugs:congeners and conjugates-a review[J]. J Biomed Sci, 2019, 26(1):84. DOI
[43]	HANSHAOWORAKUL W, SIMMERMAN J M, NARUEPONJIRAKUL U, et al. Severe human influenza infections in Thailand:oseltamivir treatment and risk factors for fatal outcome[J]. PLoS One, 2009, 4(6):e6051. DOI URL
[44]	LI Y, LIN Z, ZHAO M, et al. Silver nanoparticle based codelivery of oseltamivir to inhibit the activity of the H1N1 influenza virus through ROS-mediated signaling pathways[J]. ACS Appl Mater Interfaces, 2016, 8(37):24385-24393. DOI URL
[45]	LI Y, LIN Z, GUO M, et al. Inhibitory activity of selenium nanoparticles functionalized with oseltamivir on H1N1 influenza virus[J]. Int J Nanomedicine, 2017, 12:5733-5743. DOI URL
[46]	LI Y, LIN Z, GUO M, et al. Inhibition of H1N1 influenza virus-induced apoptosis by functionalized selenium nanoparticles with amantadine through ROS-mediated AKT signaling pathways[J]. Int J Nanomedicine, 2018, 13:2005-2016. DOI URL
[47]	LIN Z, LI Y, GONG G, et al. Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathway[J]. Int J Nanomedicin, 2018, 13:5787-5797. DOI URL

RNA片段^①	编码的蛋白质	蛋白质功能
1	PB2	RNA聚合酶组分，参与病毒遗传物质的复制和转录
2	PB1	RNA聚合酶组分，参与病毒遗传物质的复制和转录
3	PA	RNA聚合酶组分，参与病毒遗传物质的复制和转录
4	HA	血凝素，介导病毒吸附和病毒包膜-内体膜融合
5	NP	核蛋白，参与构成核糖核蛋白，参与病毒RNA的合成
6	NA	神经氨酸酶，清除细胞表面的唾液酸，防止病毒颗粒聚集，促进病毒的释放
7	MP（包括M1、M2）	M1为基质蛋白，促进病毒装配，维持病毒的形态；M2为离子通道型跨膜蛋白，促进病毒脱壳
8	NS（包括NS1、NS2）	非结构蛋白；NS1可抑制mRNA前体的拼接和干扰素产生，NS2可促进病毒RNA的表达及转运。

RNA片段^①	编码的蛋白质	蛋白质功能
1	PB2	RNA聚合酶组分，参与病毒遗传物质的复制和转录
2	PB1	RNA聚合酶组分，参与病毒遗传物质的复制和转录
3	PA	RNA聚合酶组分，参与病毒遗传物质的复制和转录
4	HA	血凝素，介导病毒吸附和病毒包膜-内体膜融合
5	NP	核蛋白，参与构成核糖核蛋白，参与病毒RNA的合成
6	NA	神经氨酸酶，清除细胞表面的唾液酸，防止病毒颗粒聚集，促进病毒的释放
7	MP（包括M1、M2）	M1为基质蛋白，促进病毒装配，维持病毒的形态；M2为离子通道型跨膜蛋白，促进病毒脱壳
8	NS（包括NS1、NS2）	非结构蛋白；NS1可抑制mRNA前体的拼接和干扰素产生，NS2可促进病毒RNA的表达及转运。