细菌脂多糖对肠道病毒71型感染影响的初步研究
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摘要
肠道病毒71型(enterovirus 71, EV71)感染常导致婴幼儿手足口病(hand, foot and mouth disease, HFMD),细菌脂多糖(lipopolysaccharide, LPS)在多种肠道病毒感染过程中起重要作用。本研究旨在探讨细菌LPS对EV71感染的影响。将EV71与LPS共孵育,测定病毒被热处理后残留病毒的活力,以及病毒感染过程中病毒基因拷贝数的变化。结果显示,热处理后病毒活力逐渐丧失,而经LPS处理的病毒活力丧失的速度减缓,且残留病毒活力与LPS浓度呈正相关;LPS处理后的病毒在黏附、侵入、胞内复制及释放过程中基因拷贝数较对照组均降低;免疫印迹分析表明LPS与抗VP1单克隆抗体可竞争性结合EV71,且粪便中的EV71可被抗大肠埃希菌抗体识别。上述结果提示,LPS可增强EV71热稳定性,抑制EV71感染过程,且LPS可能与EV71结合。
Enterovirus 71(EV71) infection mainly causes hand-foot-mouth disease(HFMD) in infants and young children. There are many commensal bacteria in the environment of viral infection. It was reported that lipopolysaccharide(LPS) plays an important role in some enterovirus infections. This study aims to investigate the effects of LPS on EV71 infection. EV71 was co-incubated with LPS to determine its impact on the viral viability and infectivity. Results showed that LPS-incubated EV71 lost their viability slower than that of the EV71 control in a LPS concentration-dependent manner. In contrast, the infectivity of EV71 decreased when the virus was pretreated by LPS. The immunoblotting assay showed that LPS could bind with EV71 competitively with anti-VP1. EV71 from HFMD patients can be detected by anti-E.coli antibodies. The observations indicated that LPS can increase the thermal stability of EV71 and inhibit viral infection. Both effects might be ascribed to the capability of LPS binding with the virus.
Enterovirus 71(EV71) infection mainly causes hand-foot-mouth disease(HFMD) in infants and young children. There are many commensal bacteria in the environment of viral infection. It was reported that lipopolysaccharide(LPS) plays an important role in some enterovirus infections. This study aims to investigate the effects of LPS on EV71 infection. EV71 was co-incubated with LPS to determine its impact on the viral viability and infectivity. Results showed that LPS-incubated EV71 lost their viability slower than that of the EV71 control in a LPS concentration-dependent manner. In contrast, the infectivity of EV71 decreased when the virus was pretreated by LPS. The immunoblotting assay showed that LPS could bind with EV71 competitively with anti-VP1. EV71 from HFMD patients can be detected by anti-E.coli antibodies. The observations indicated that LPS can increase the thermal stability of EV71 and inhibit viral infection. Both effects might be ascribed to the capability of LPS binding with the virus.
引文
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[2] Chang LY,Huang LM,Gau SS,Wu YY,Hsia SH,Fan TY,Lin KL,Huang YC,Lu CY,Lin TY.Neurodevelopment and cognition in children after enterovirus 71 infection [J].N Engl J Med,2007,356(12):1226-1234.
[3] Huang CC,Liu CC,Chang YC,Chen CY,Wang ST,Yeh TF.Neurologic complications in children with enterovirus 71 infection [J].N Engl J Med,1999,341(13):936-942.
[4] Zhou Y,Li JX,Jin PF,Wang YX,Zhu FC.Enterovirus 71:a whole virion inactivated enterovirus 71 vaccine [J].Expert Rev Vaccines,2016,15(7):803-813.
[5] Wu KX,Ng MM,Chu JJ.Developments towards antiviral therapies against enterovirus 71 [J].Drug Discov Today,2010,15(23-24):1041-1051.
[6] Qin J,Li R,Raes J,Arumugam M,Burgdorf KS,Manichanh C,Nielsen T,Pons N,Levenez F,Yamada T,Mende DR,Li J,Xu J,Li S,Li D,Cao J,Wang B,Liang H,Zheng H,Xie Y,Tap J,Lepage P,Bertalan M,Batto JM,Hansen T,Le Paslier D,Linneberg A,Nielsen HB,Pelletier E,Renault P,Sicheritz-Ponten T,Turner K,Zhu H,Yu C,Li S,Jian M,Zhou Y,Li Y,Zhang X,Li S,Qin N,Yang H,Wang J,Brunak S,Doré J,Guarner F,Kristiansen K,Pedersen O,Parkhill J,Weissenbach J;MetaHIT Consortium;Bork P,Ehrlich SD,Wang J.A human gut microbial gene catalogue established by metagenomic sequencing [J].Nature,2010,464(7285):59-65.
[7] Karst SM.The influence of commensal bacteria on infection with enteric viruses [J].Nat Rev Microbiol,2016,14(4):197-204.
[8] Berger AK,Yi H,Kearns DB,Mainou BA.Bacteria and bacterial envelope components enhance mammalian reovirus thermostability [J].PLoS Pathog,2017,13(12):e1006768.
[9] Lu J,He YQ,Yi LN,Zan H,Kung HF,He ML.Viral kinetics of enterovirus 71 in human abdomyosarcoma cells [J].World J Gastroenterol,2011,17(36):4135-4142.
[10] Norman JM,Handley SA,Virgin HW.Kingdom-agnostic metagenomics and the importance of complete characterization of enteric microbial communities [J].Gastroenterology,2014,146(6):1459-1469.
[11] Kuss SK,Best GT,Etheredge CA,Pruijssers AJ,Frierson JM,Hooper LV,Dermody TS,Pfeiffer JK.Intestinal microbiota promote enteric virus replication and systemic pathogenesis [J].Science,2011,334(6053):249-252.
[12] Robinson CM,Jesudhasan PR,Pfeiffer JK.Bacterial lipopolysaccharide binding enhances virion stability and promotes environmental fitness of an enteric virus [J].Cell Host Microbe,2014,15(1):36-46.
[13] Walter TS,Ren J,Tuthill TJ,Rowlands DJ,Stuart DI,Fry EE.A plate-based high-throughput assay for virus stability and vaccine formulation [J].J Virol Methods,2012,185(1):166-170.
[14] Waldman P,Meseguer A,Lucas F,Moulin L,Wurtzer S.Interaction of human enteric viruses with microbial compounds:implication for virus persistence and disinfection treatments [J].Environ Sci Technol,2017,51(23):13633-13640.
[15] Kane M,Case LK,Kopaskie K,Kozlova A,MacDearmid C,Chervonsky AV,Golovkina TV.Successful transmission of a retrovirus depends on the commensal microbiota [J].Science,2011,334(6053):245-249.
[16] Jude BA,Pobezinskaya Y,Bishop J,Parke S,Medzhitov RM,Chervonsky AV,Golovkina TV.Subversion of the innate immune system by a retrovirus [J].Nat Immunol,2003,4(6):573-578.
[17] Wilks J,Lien E,Jacobson AN,Fischbach MA,Qureshi N,Chervonsky AV,Golovkina TV.Mammalian lipopolysaccharide receptors incorporated into the retroviral envelope augment virus transmission [J].Cell Host Microbe,2015,18(4):456-462.