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1、Chapter 27 EnterovirusesIntroduction nEnteroviruses are small viruses that are made of single-stranded linear RNA and protein. nThis group includes the polioviruses(脊髓灰质炎病毒), coxsackieviruses(柯萨奇病毒), echoviruses(埃可病毒), and other enteroviruses.nEnteroviruses are transmitted predominantly via the feca
2、l/oral route(粪口途径), although respiratory-oral spread and spread by fomites are also possible. 第一节 脊髓灰质炎病毒Poliovirusn该病毒是脊髓灰质炎的病原体。n侵犯脊髓前角运动神经细胞，导 致弛缓型肢体麻痹。n多见于儿童，故亦称小儿麻痹症 。nCubic symmetry, no envelopen+ssRNAnStructural protein: VP1-VP4nClassified by antigen C and D nSurvive for months in feces and s
3、ewageVirology脊髓灰质炎病毒脊髓灰质炎病毒颗粒负染电镜照片 Antigenic properties and sensitivitynThree serotypes: VP1,VP2,VP3. nVP1 is the most common form encountered in nature, however all three forms are extremely infectious. nMinimal heterotypic immunity between serotypes.nRapidly inactivated by heat, chlorine, ultravi
4、olet light.结构蛋白的功能nVP1、VP2、VP3在病毒表面，VP4在病毒衣壳内部nVP1、VP2、VP3可诱导中和抗体产生nVP1与病毒吸附到细胞表面特异性受体有关nVP4参与维持病毒的空间构型及病毒的脱壳过程PathogenesisSource of infection: Apparent and inapparent patientsTransmission: - fecal-oral route, by ingesting contaminated food or water- oral-oral route, a mode especially visible in are
5、as with good sanitation and hygiene.nEntry into mouthnReplication in pharynx, GI tract, local lymphaticsnHematologic spread to lymphatics and central nervous systemnViral spread along nerve fibresnDestruction of motor neuronsPathogenesisThree possible outcomes of poliovirus infection:u Subclinical i
6、nfection (90 - 95%) subclinical (inapparent) infection account for the vast majority of poliovirus infections. u Abortive infection (4 - 8%) - a minor influenza- like illness occurs, recovery occurs within a few days and the diagnosis can only be made by the laboratory. The minor illness may be acco
7、mpanied by aseptic meningitis.u Major illness (1 - 2%) - the major illness may present 2 - 3 days following the minor illness or without any preceding minor illness. Signs of aseptic meningitis are common. Involvement of the anterior horn cells lead to flaccid paralysis. Involvement of the medulla m
8、ay lead to respiratory paralysis and death. 所致疾病90%以上为隐性感染 (Subclinical infection) 5%感染者发生顿挫感染 (Abortive infection) 1%-2%感染者出现非麻痹型脊髓灰质炎或无 菌性脑膜炎0.1%-0.2%感染者出现暂时性肢体麻痹或永 久性弛缓性肢体麻痹极少数患者发展为延髓麻痹，导致呼吸、 心脏衰竭死亡。脊髓灰质炎A child displaying a deformity of her right lower extremity due to polio. 脊髓灰质炎致病机制粪口途径传播以上呼吸
9、道，咽喉 ，肠道为侵入门户先在局部 粘膜和淋 巴结中增 殖入血， 形成第 一次病 毒血症带有受体的靶组织增殖后形成第 二次病毒血症 及临床症状双份血清ELISA补体结合试验中和试验血清学检查：病毒分离检查：细胞培养PCR法Lab diagnosisPrevention人工主动免疫OPVIPV（口服减毒活疫苗）（注射死疫苗）类似自然感染途径 刺激肠道局部产生SIgA 产生间接免疫优点均为三价疫苗nOral Poliovirus Vaccine (OPV)nConsists of live attenuated virus of all 3 serotypes. nProduces local i
10、mmunity through the induction of an IgA response as well as systemic immunity.nRarely causes paralytic poliomyelitis, around 1 in 3 million doses.PreventionAn infant in India gets the polio vaccine. 项目 活疫苗 （OPV） 死疫苗 （IPV）接种方法 口服糖丸 肌肉注射抗体产生 血清抗体、分泌抗体 血清抗体 间接免疫 能通过接种者粪便排毒免疫更多人群 稳定性 差,不易保存 易保存副作用 极少数引起
11、疫苗相关脊髓灰质炎免疫效果 更好 好脊髓灰质炎死活苗的比较Other enteroviruses n Coxsackievirusesn Echoviruses n New enterovirus typesn生物学形状同肠道病毒的共同特性n识别的受体在组织细胞中分布广泛n致病特点是在肠道中增殖，却很少引起肠道疾病n不同的型别可引起相同的临床综合症，同型病毒也可引起不同的临床疾病Coxsackie Virus（柯萨奇病毒）q据对新生乳鼠的致病性不同，分A组和B组nA组病毒：诱发新生乳鼠弥漫性骨胳肌炎，导致驰缓性麻痹nB组病毒：诱发新生乳鼠局灶性骨胳肌炎，导致痉挛性麻痹q 预防尚无疫苗可用柯萨奇
12、病毒B4Echo Virus（埃可病毒）n 不诱发新生乳鼠病变n 诱发婴儿腹泻和无菌性脑膜炎等 人类疾患n Enterovirus 71 appears to be highly pathogenic and has been associated with epidemics of a variety of acute diseases, including aseptic meningitis, encephalitis, paralytic poliomyelitis-like disease and hand-foot-mouth disease. New EnterovirusesP
13、athogenesisnAseptic meningitis, Encephalitis, Paralytic Disease 无菌性脑膜炎、脑炎、轻 瘫nHerpangina 疱疹性咽峡炎nHFMD 手足口病nEpidemic pleurodynia 流行性胸痛nMyocarditis and pericarditis 心肌炎和心包 炎nConjunctivitis 结膜炎nPancreatitis/Diabetes 胰腺炎和糖尿病疱疹性咽峡炎Hand, foot, and mouth disease (HFMD)nHFMD is a common illness of infants an
14、d children caused by coxsackie virus A16, enterovirus 71 (EV71) and other enteroviruses.nIt is characterized by fever, sores/ulcers in the mouth feet. The rashes may also appear on buttocks and on the legs and arms. The ulcers in the mouth usually appear, and a rash with blisters. The blisters may a
15、ppear in the mouth, palms of the hands and soles of the on the tongue, the sides of the cheeks, gums or near the throat. 什么是手足口病?手足口病（Hand-foot-mouth disease, HFMD）是由肠道病毒感染引起的临床症候群，具有临床 表现多样的特点，多数病例临床表现较轻，以发热 和手、足、口腔等部位的皮疹或疱疹为主要特征。 少数病例出现呼吸系统、中枢神经系统损害，引起 脑炎、心肌炎、肺水肿、弛缓性麻痹等症状，个别 重症患儿病情进展快，导致死亡。Blister on the palms of the handBlister on the dorsum of the feetBlister on the soles of the feetBlister then become ulcer on the inner gums Hand, foot, and mouth disease (HFMD) 临床症状n大多数患者症状轻微,以发热和手、足、口 腔等部位的皮疹或疱疹为主要特征。n少数患者可并发无菌性脑膜炎、脑炎、急 性弛缓性麻痹、呼吸道感染和心肌炎等。n个别重症患儿病情进展快,易发生死亡。n少年儿童和成人感染后多不发病,但能够传
