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1、Department of Microbiology, Harbin Medical UniversityDepartment of Microbiology, Harbin Medical UniversityMedical MicrobiologyMedical Microbiology 医医 学学 微微 生生 物物 学学Department of Microbiology, HMUDepartment of Microbiology, HMU 哈尔滨医科大学微生物学教研室哈尔滨医科大学微生物学教研室Department of Microbiology, Harbin Medical Un
2、iversity第三篇 医学相关病毒第34章 出血热病毒Haemorrhagic Fever virus微生物学教研室 宋武琦Department of Microbiology, Harbin Medical University教学大纲n掌握内容u汉坦病毒主要生物学性状，包括形态结构、 培养特性、抗原分型及抵抗力；流行环节及 致病性;微生物学检查法。 新疆出血热病毒致 病性及传播媒介 n了解内容u肾综合征出血热病毒及新疆出血热病毒防治 原则；非洲出血热病毒（埃博拉病毒和马堡 热病毒）的传播方式及引起疾病 Department of Microbiology, Harbin Medical
3、UniversityHistorynHaemorrhagic Fever with Renal Syndrome (HFRS: later renamed hantavirus disease, HVD) first recognized in Heilongjiang, China in the 1930s, and came to the attention of the West during the Korean war when over 3000 UN troops were afflictednIt transpired that the disease was not new
4、and had been described by the Chinese 1000 years earlier In 1974, the causative was isolated from the Korean Stripped field mice and was called Hantaan virus In 1995, a new disease entity called hantavirus pulmonary syndrome was described in the “four corners” region of the U.S.Department of Microbi
5、ology, Harbin Medical University病毒体病毒体 VirionVirionnForms a separate genus in the Bunyavirus family 布尼雅 病毒科nUnlike other bunyaviridae, its transmission does not involve an arthropod vectornEnveloped -ssRNA virusnVirions 98nm in diameter with a characteristic square grid- like structure.nGenome consi
6、sts of three RNA segments: L, M, and S.Department of Microbiology, Harbin Medical University基于中和试验的血清型基于中和试验的血清型 Subtypes ofSubtypes of Hantaviruses Hantaviruses Based NT Based NTn黑线姬鼠型n褐家鼠型n欧洲棕背鼠型n草原田鼠型n巴尔干姬鼠型n小家鼠型黑线姬黑线姬田鼠田鼠小家鼠小家鼠Department of Microbiology, Harbin Medical University根据抗原和基因结构分型（根据抗原
7、和基因结构分型（1010型）型）nHantaan（汉滩型）nSeoul type（汉城型）nPuumala type nSin Nombre（辛诺柏型）Department of Microbiology, Harbin Medical University流行病毒学流行病毒学 EpidemiologyEpidemiologynNatural host: Rodent Apodemus agrarius (Stripped field mice, 黑线姬鼠)n传染源：黑线姬鼠、褐家鼠、大林姬鼠nViral contamination comes from rodent urine, stool
8、, salivary secretionnSeasonal and regional distribution (autumn and winter, Oct.-Jan.)nThe infection route is still uncertain. The possible entries are respiratory tract, mouth, and direct contactRodent Carriers ofRodent Carriers of Hantaviruses HantavirusesStripped field mouse (Apodemus agrarius) B
9、ank vole (Clethrionomys glareolus)Deer Mouse (Peromyscus maniculatus) Rat (Rattus)Department of Microbiology, Harbin Medical University临床特点临床特点 Clinical FeaturesClinical FeaturesnIncubation: 2 weeks, HFRSnPathogenesis mechanism is unknown. Immunological reaction may play rolen极低的隐性感染率 Very low subcl
10、inical infection rate (1-4%) n病后稳定的免疫力，一般不再发病 Stable humoral immunity. no repeat infectionDepartment of Microbiology, Harbin Medical University致病性致病性 PathogenesisPathogenesisnThe multisystem pathology of HVD is characterized by damage to capillaries and small vessel walls, resulting in vasodilation
11、and congestion with hemorrhagesnClassically, hantavirus disease consists of 5 distinct phases. These phases may be blurred in moderate or mild casesDepartment of Microbiology, Harbin Medical UniversitynFebrile phase 发热期 nHypotensive phase 低血压期nOliguric phase 少尿期nDiuretic phase 多尿期nConvalescent phase
12、 恢复期Department of Microbiology, Harbin Medical UniversityComparative Clinical Features of Comparative Clinical Features of Recognized Recognized HantavirusHantavirus Disease (HVD) Disease (HVD)Department of Microbiology, Harbin Medical University汉坦病毒肺综合征汉坦病毒肺综合征 HantavirusHantavirus Pulmonary Syndro
13、me Pulmonary SyndromenThe majority of cases are caused by the Sin Nombre virus（汉坦病毒属辛诺柏病毒）nMore than 250 cases of HPS have been reported throughout North and South America with a mortality rate of 50%Department of Microbiology, Harbin Medical University诊断诊断 DiagnosisDiagnosisn血清学诊断 n直接检测病毒抗原nRT-PCRn
14、病毒分离 Virus isolationn免疫组化Department of Microbiology, Harbin Medical University治疗和预防治疗和预防nTreatment of HVD and HPS depends mainly on supportive measures 支持疗法nRibavirin 利巴韦林nVaccinationnRodent ControlDepartment of Microbiology, Harbin Medical University新疆出血热病毒 Xinjiang Hemorrhagic Fever Virusn1966年首次从
15、新疆塔里木盆地出血热病 人血液、尸体脏器及硬蜱中分离n流行病学及病毒抗原性u与克里米亚-刚果出血热病毒（Crimean- Congo hemorrhagic hever virus，CCHFV） 相似uXHFV与CCHFV同种，属布尼雅病毒科（ Bunyaviridae）内罗病毒属（nairovirus）Department of Microbiology, Harbin Medical University生物学性状 n球形或椭圆形，直径为90nm 120nm，外有包膜，表面有空管 样突起n病毒基因组为分节段的-ssRNAn出生后l4天的乳鼠对XHFV最为 敏感，常用于病毒分离及传代。 用V
16、ero E6等细胞培养病毒不产生 CPE，可用免疫荧光法通过检测n感染细胞的胞浆内可形成嗜碱性 包涵体Department of Microbiology, Harbin Medical University致病性与免疫性n野生动物（啮齿类动物）和家畜（羊、牛、马、 骆驼、狐狸和兔）是自然宿主和传染源。羊在维 持XHF疫原上起重要作用n硬蜱特别是亚洲璃眼蜱（hyalomma asiaticum） 是传播媒介。病毒在蜱体内增殖并经卵传给子代 ，蜱也是病毒的长期储存宿主Department of Microbiology, Harbin Medical Universityn蜱在每年的4月6月大量增殖u人群发病的高峰u蜱叮咬或与病畜直接接触（破损皮肤）感染n57天潜伏期发病，以发热和出血为特征n产生中和（NT）抗体、血凝抑制抗体uNT抗体出现较早，维持较久u病后可获得持久免疫力Department of Microbiology, Harbin M
