2018-2020年广州急性呼吸道感染患儿中腺病毒分子流行病学特征研究Molecular Epidemiological Characteristics of Adenoviruses in Children with Acute Respiratory Tract Infection in Guangzhou,China,from 2018 to 2020
周吉剑;李万维;于博;王烟岚;薛豹;李弘剑;
摘要(Abstract):
为了解2018-2020年间广州地区急性呼吸道感染儿童中腺病毒的流行病学特征,收集广东省妇幼保健院番禺院区和暨南大学附属第一医院儿科住院部急性呼吸道感染患儿咽拭子标本,采用荧光定量PCR技术检测腺病毒核酸,分析腺病毒的流行病学特征。所有腺病毒阳性标本接种A549细胞进行病毒分离,获得临床分离株后,对不同型别分离株的生长特点进行研究,并比较了感染患儿的临床特征。结果显示,在收集的701份急性呼吸道感染患儿的咽拭子标本中,腺病毒阳性率为4.99%(35/701),易感人群为5岁以下儿童。系统发育分析显示主要型别为B种3型腺病毒(42.86%)与B种7型腺病毒(14.29%)。经细胞培养后获得腺病毒阳性毒株28株,分离率为80%。临床分离株感染特征分析结果显示,PCR检测B种7型腺病毒分离株病毒基因组拷贝数显著高于其他基因型。对感染患儿临床特征的分析显示,B种3型腺病毒感染患儿中性粒细胞增高伴淋巴细胞降低。上述结果表明,2018-2020年间急性呼吸道感染的住院儿童腺病毒阳性患儿中,B种3型与B种7型为优势流行基因型,病毒基因进化高度保守。临床分离株中,B种7型腺病毒生长速率较高。
关键词(KeyWords): 人腺病毒;急性呼吸道感染;Hexon;Fiber
基金项目(Foundation): “十三五”国家传染病防治重大专项(项目号:2017ZX10103011-007),题目:珠三角地区儿童传染病重要症候群病原谱及危害重症病原特征研究~~
作者(Authors): 周吉剑;李万维;于博;王烟岚;薛豹;李弘剑;
DOI: 10.13242/j.cnki.bingduxuebao.004196
参考文献(References):
- [1]Brealey J C,Sly P D,Young P R,Chappell K J. Viral bacterial co-infection of the respiratory tract during early childhood[J/OL]. FEMS Microbiol Lett,2015,362(10):551-556.DOI:10.1093/femsle/fnv062.
- [2]Buckwalter S P,Teo R,Espy M J,Sloan L M,Smith T F,Pritt B S. Real-time qualitative PCR for 57 human adenovirus types from multiple specimen sources[J/OL]. J Clin Microbiol,2012,50(3):766-771. DOI:10.1128/JCM.05629-11.
- [3]Lynch J P, 3rd, Kajon A E. Adenovirus:Epidemiology,Global Spread of Novel Serotypes,and Advances in Treatment and Prevention[J/OL]. Semin Respir Crit Care Med,2016,37(4):586-602. DOI:10.1055/s-0036-1584923.
- [4]Rowe W P,Huebner R J,Gilmore L K,Parrott R H,Ward T G. Isolation of a cytopathogenic agent from human adenoids undergoing spontaneous degeneration in tissue culture[J/OL]. Proc Soc Exp Biol Med,1953,84(3):570-573.DOI:10.3181/00379727-84-20714.
- [5]Hilleman M R,Werner J H. Recovery of new agent from patients with acute respiratory illness[J/OL]. Proc Soc Exp Biol Med,1954,85(1):183-188. DOI:10.3181/00379727-85-20825.
- [6]Aoki K, Benko M, Davison A J, Echavarria M,Erdman D D,Harrach B,Kajon A E,Schnurr D,Wadell G,Members of the Adenovirus Research C.Toward an integrated human adenovirus designation system that utilizes molecular and serological data and serves both clinical and fundamental virology[J/OL]. J Virol, 2011, 85(11):5703-5704. DOI:10.1128/JVI.00491-11.
- [7]San Martin C. Latest insights on adenovirus structure and assembly[J/OL]. Viruses,2012,4(5):847-877.DOI:10.3390/v4050847.
- [8]Takeuchi S, Itoh N, Uchio E, Aoki K, Ohno S.Serotyping of adenoviruses on conjunctival scrapings by PCR and sequence analysis[J/OL]. J Clin Microbiol,1999,37(6):1839-1845.DOI:10.1128/JCM.37.6.1839-1845.1999.
- [9]Lu X, Erdman D D. Molecular typing of human adenoviruses by PCR and sequencing of a partial region of the hexon gene[J/OL]. Arch Virol,2006,151(8):1587-1602.DOI:10.1007/s00705-005-0722-7.
- [10]Walsh M P,Seto J,Jones M S,Chodosh J,Xu W,Seto D. Computational analysis identifies human adenovirus type 55 as a re-emergent acute respiratory disease pathogen[J/OL]. J Clin Microbiol,2010,48(3):991-993.DOI:10.1128/JCM.01694-09.
- [11]Heim A,Ebnet C,Harste G,Pring-Akerblom P. Rapid and quantitative detection of human adenovirus DNA by real-time PCR[J/OL]. J Med Virol,2003,70(2):228-239.DOI:10.1002/jmv.10382.
- [12]Brini I,Guerrero A,Ezzine I K,H?ller D O,Hetzer B,Würzner R,Hazgui O,Handous I,Merchaoui S N,Bouguila J, Mahdhaoui N, Boughamoura L,Malekshahi Z,Laer D v,Hannachi N,Boukadida J,Stoiber H. Human adenoviruses associated with respiratory illness in neonates,infants,and children in the Sousse area of Tunisia[J/OL]. J Med Virol,2020(6):145-151.DOI:10.1002/jmv.26375.
- [13]Dhingra A,Hage E,Ganzenmueller T,Bottcher S,Hofmann J, Hamprecht K, Obermeier P, Rath B,Hausmann F,Dobner T,Heim A. Molecular Evolution of Human Adenovirus(HAdV)Species C[J/OL]. Sci Rep,2019,9(1):1039. DOI:10.1038/s41598-018-37249-4.
- [14]Kajon A E,Lu X,Erdman D D,Louie J,Schnurr D,George K S,Koopmans M P,Allibhai T,Metzgar D.Molecular epidemiology and brief history of emerging adenovirus 14-associated respiratory disease in the United States[J/OL]. J Infect Dis,2010,202(1):93-103.DOI:10.1086/653083.
- [15]Palomino M A,Larranaga C,Avendano L F. Hospitalacquired adenovirus 7h infantile respiratory infection in Chile[J/OL]. Pediatr Infect Dis J,2000,19(6):527-531.DOI:10.1097/00006454-200006000-00007.
- [16]Xie L,Yu X F,Sun Z,Yang X H,Huang R J,Wang J,Yu A,Zheng L,Yu M C,Hu X W,Wang B M,Chen J,Pan J C,Liu S L. Two adenovirus serotype 3outbreaks associated with febrile respiratory disease and pharyngoconjunctival fever in children under 15 years of age in Hangzhou,China,during 2011[J/OL]. J Clin Microbiol,2012,50(6):1879-1888. DOI:10.1128/JCM.06523-11.
- [17]Biere B, Schweiger B. Human adenoviruses in respiratory infections:sequencing of the hexon hypervariable region reveals high sequence variability[J/OL]. J Clin Virol, 2010, 47(4):366-371. DOI:10.1016/j.jcv.2010.01.005.
- [18]Lafolie J, Mirand A, Salmona M, Lautrette A,Archimbaud C,Brebion A,Regagnon C,Chambon M,Mercier-Delarue S,Le Goff J,Henquell C. Severe pneumonia associated with adenovirus type 55 infection,France, 2014[J/OL]. Emerg Infect Dis, 2016, 22(11):2012-2014.DOI:10.3201/eid2211.160728.
- [19]Zhang S Y,Luo Y P,Huang D D,Fan H,Lu Q B,Wo Y,Chen G,Zhang X A,Li Y,Tong Y G,Cao W C,Liu W. Fatal pneumonia cases caused by human adenovirus 55 in immunocompetent adults[J/OL].Infect Dis(Lond),2016,48(1):40-47.DOI:10.3109/23744235.2015.1055585.
- [20]Carr M J,Kajon A E,Lu X,Dunford L,O'Reilly P,Holder P,De Gascun C F,Coughlan S,Connell J,Erdman D D,Hall W W. Deaths associated with human adenovirus-14p1 infections,Europe,2009-2010[J/OL]. Emerg Infect Dis,2011,17(8):1402-1408.DOI:10.3201/eid1708.101760.
- [21]Hong J Y,Lee H J,Piedra P A,Choi E H,Park K H,Koh Y Y,Kim W S. Lower respiratory tract infections due to adenovirus in hospitalized Korean children:epidemiology,clinical features,and prognosis[J/OL].Clin Infect Dis, 2001, 32(10):1423-1429. DOI:10.1086/320146.
- [22]Zou L,Zhou J,Li H,Wu J,Mo Y,Chen Q,Fang L,Wu D,Wu J,Ke C. Human adenovirus infection in children with acute respiratory tract disease in Guangzhou,China[J/OL]. APMIS,2012,120(8):683-688.DOI:10.1111/j.1600-0463.2012.02890.x.
- [23]Yao L H,Wang C,Wei T L,Wang H,Ma F L,Zheng L S. Human adenovirus among hospitalized children with respiratory tract infections in Beijing,China,2017-2018[J/OL]. Virol J,2019,16(1):78.DOI:10.1186/s12985-019-1185-x.
- [24]Wang H,Zheng Y,Deng J,Chen X,Liu P,Li X.Molecular epidemiology of respiratory adenovirus detection in hospitalized children in Shenzhen,China[J/OL]. Int J Clin Exp Med,2015,8(9):15011-15017.DOI:10.1109/PEDS.2015.7203404.
- [25]Li L,Woo Y Y,de Bruyne J A,Nathan A M,Kee S Y,Chan Y F,Chiam C W,Eg K P,Thavagnanam S,Sam I C. Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur,Malaysia[J/OL]. PLoS One,2018,13(10):232-239.DOI:10.1371/journal.pone.0205795.
- [26]James L,Vernon M O,Jones R C,Stewart A,Lu X,Zollar L M,Chudoba M,Westercamp M,Alcasid G,Duffee-Kerr L,Wood L,Boonlayangoor S,Bethel C,Ritger K, Conover C, Erdman D D, Gerber S I.Outbreak of human adenovirus type 3 infection in a pediatric long-term care facility--Illinois,2005[J/OL].Clin Infect Dis,2007,45(4):416-420.DOI:10.1086/519938.
- [27]Binder A M,Biggs H M,Haynes A K,Chommanard C,Lu X,Erdman D D,Watson J T,Gerber S I.Human adenovirus surveillance-United States,2003-2016[J/OL]. MMWR Morb Mortal Wkly Rep,2017,66(39):1039-1042.DOI:10.15585/mmwr.mm6639a2.
- [28]Qurei L,Seto D,Salah Z,Azzeh M. A molecular epidemiology survey of respiratory adenoviruses circulating in children residing in Southern Palestine[J/OL]. PLoS One,2012,7(8):57-63. DOI:10.1371/journal.pone.0042732.
- [29]Li H,Liu G S,Shi Y,Niu P H,Jiang S Y,Xu L L,Lu R J,Zhao S C,Tan W J. Epidemic and molecular characteristic of human adenovirus infection among patients with febrile respiratory syndrome from a hospital in Qinghai Province,2012-2015[J/OL]. Zhonghua Yu Fang Yi Xue Za Zhi,2017,51(7):650-652. DOI:10.3760/cma.j.issn.0253-9624.2017.07.014.
- [30]Han G,Niu H,Zhao S,Zhu B,Wang C,Liu Y,Zhang M, Yang S, Liu F, Wan C, Zhang Q.Identification and typing of respiratory adenoviruses in Guangzhou,Southern China using a rapid and simple method[J/OL]. Virol Sin,2013,28(2):103-108.DOI:10.1007/s12250-013-3308-7.
- [31]Fu Y,Tang Z,Ye Z,Mo S,Tian X,Ni K,Ren L,Liu E, Zang N. Human adenovirus type 7 infection causes a more severe disease than type 3[J/OL]. BMC Infect Dis,2019,19(1):36.DOI:10.1186/s12879-018-3651-2.
- [32]Zahradnik J M. Adenovirus pneumonia[J/OL]. Semin Respir Infect,1987,2(2):104-111. DOI:10.1111/j.1445-5994.1973.tb04306.x.
- [33]Carballal G,Videla C,Misirlian A,Requeijo P V,Aguilar Mdel C. Adenovirus type 7 associated with severe and fatal acute lower respiratory infections in argentine children[J/OL]. BMC Pediatr,2002,2:6.DOI:10.1186/1471-2431-2-6.
- [34]Wang H,Li Z Y,Liu Y,Persson J,Beyer I,Moller T,Koyuncu D,Drescher M R,Strauss R,Zhang X B,Wahl J K,3rd,Urban N,Drescher C,Hemminki A,Fender P,Lieber A. Desmoglein 2 is a receptor for adenovirus serotypes 3,7,11 and 14[J/OL]. Nat Med,2011,17(1):96-104.DOI:10.1038/nm.2270.
- [35]Feng Y,Yi C,Liu X,Qu L,Su W,Shu T,Zheng X,Ye X,Luo J,Hao M,Sun X,Li L,Liu X,Yang C,Guan S,Chen L,Feng L. Human desmoglein-2 and human CD46 mediate human adenovirus type 55infection,but human desmoglein-2 plays the major roles[J/OL]. J Virol, 2020, 94(17). DOI:10.1128/JVI.00747-20.
- [36]Roelvink P W,Lizonova A,Lee J G,Li Y,Bergelson J M,Finberg R W,Brough D E,Kovesdi I,Wickham T J. The coxsackievirus-adenovirus receptor protein can function as a cellular attachment protein for adenovirus serotypes from subgroups A,C,D,E,and F[J/OL]. J Virol, 1998, 72(10):7909-7915. DOI:10.1128/JVI.72.10.7909-7915.1998.
- [37]Adams W C,Bond E,Havenga M J E,Holterman L,Goudsmit J,Karlsson Hedestam G B,Koup R A,Lore K. Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus-adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN[J/OL]. J Gen Virol,2009,90(Pt 7):1600-1610.DOI:10.1099/vir.0.008342-0.
- [38]Lee J, Choi E H, Lee H J. Clinical severity of respiratory adenoviral infection by serotypes in Korean children over 17 consecutive years(1991-2007)[J/OL].J Clin Virol,2010,49(2):115-120. DOI:10.1016/j.jcv.2010.07.007.
- [39]Kajon A E, Gigliotti A P, Harrod K S. Acute inflammatory response and remodeling of airway epithelium after subspecies B1 human adenovirus infection of the mouse lower respiratory tract[J/OL]. J Med Virol,2003,71(2):233-244. DOI:10.1002/jmv.10475.
- [40]Hung K H, Lin L H. Adenovirus pneumonia complicated with acute respiratory distress syndrome:a case report[J/OL]. Medicine(Baltimore),2015,94(20):776-783.DOI:10.1097/MD.0000000000000776.
- [41]Biserni G B,Dondi A,Masetti R,Bandini J,Dormi A,Conti F, Pession A, Lanari M. Immune response against adenovirus in acute upper respiratory tract infections in immunocompetent children[J/OL].Vaccines(Basel),2020,8(4):339-346.DOI:10.3390/vaccines8040602.