Flavivirus
黄 病 毒
Department of Microbiology,HMU
第 33章黄病毒、出血热病毒、狂犬病病毒问题：
什么是虫媒病毒？常见的昆虫媒介有哪些？
登革病毒的所致疾病及传播方式
流行性乙型脑炎病毒的传播环节，如何控制？
引起肾综合征出血热的病毒是什么？自然宿主是什么？如何传染给人？
狂犬病病毒的致病机制、预防原则人畜共患病毒性疾病
Viral Zoonosis
人畜共患病
脊椎动物（ vertebrate animals）所患疾病能通过昆虫媒介直接或间接传递给人类
如果有昆虫参与，这个疾病也称为虫媒疾病
（ arboviral）
如狂犬病、肾综合症出血热、流行性乙型脑炎和埃博拉出血热虫媒病毒（ Arthropod-borne viruses
,arboviruses）是通过节肢动物（
arthropod vectors）传播的病毒
The WHO definition is as follows
Viruses maintained in nature principally,
or to an important extent,through
biological transmission between
susceptible vertebrate hosts by
haematophagus arthropods or
through transovarian and possibly
venereal transmission in arthropods
虫媒病毒种类
虫媒病毒分属 3个病毒科：
Togaviruses （ 披膜病毒科 ）
EEE,WEE,and VEE
Bunyaviruses （ 布尼亚病毒科 ）
Haemorrhagic Fever
Sandfly Fever,Rift Valley Fever,Crimean-Congo
Flaviviruses （ 黄病毒科 ）
Yellow Fever,dengue,Japanese Encephalitis
在我国流行并经病毒分离证实的虫媒病有
6种
流行性乙型脑炎
森林脑炎
登革热
基孔贡亚热
肾综合征出血热
新疆出血热黄病毒 Flaviviruses
登革病毒 Dengue viruses
流行性乙型脑炎病毒 Epidemic type B
encephalitis virus
蜱传脑炎病毒 Tick-borne encephalitis virus
黄病毒生物学特性
球形,20~60nm，个别达 100nm，有包膜,+ssRNA基因组，有感染性，只有一个读码框，编码一个大前体蛋白，切割后分成结构和调节蛋白
核心由 C蛋白和 RNA构成二十面体立称 核衣壳,包膜上有病毒编码的 M和 E蛋白,其中 E蛋白具有血凝素作用,
能凝集鸡红细胞
对酸、醚,氯仿敏感
在 节肢动物体 内增殖，对节肢动物不致病，但通过叮咬传染给脊椎动物和人类，引起 自然疫源性的人畜共患疾病,脑炎、黄热病和出血热等
致病呈明显的季节性和地区性节肢动物媒介
Arthropod Vectors
Mosquitoes （ 蚊 ）
Japanese encephalitis,dengue,yellow fever,St,
Louis encephalitis,etc.
Ticks （ 虱,蜱 ）
Crimean-Congo haemorrhagic fever,various tick-
borne encephalitis etc.
Sandflies （ 白蛉 ）
Sicilian sandfly fever,Rift valley fever.
Arthropod Vectors
Aedes Aegyti （ 伊蚊 ） Assorted Ticks （ 虱、蜱 ）
Phlebotmine Sandfly （ 吸血白蛉 ）Culex Mosquito （ 库蚊 ）
动物宿主（ Reservoirs）
In many cases,the actual reservoir is not known,The
following animals are implicated as reservoirs
鸟
Japanese encephalitis,St Louis encephalitis
猪
Japanese encephalitis
猴
Yellow Fever
啮齿类动物
Russian Spring-Summer encephalitis
传播环节
人 – 节肢动物 – 人
Dengue
动物 – 节肢动物 – 人
Japanese Encephalitis
混合方式：两种都有
some arboviruses such as yellow fever
Man-Arthropod-Man Cycle
Dengue
Reservoir may be in either man or arthropod vector
In the latter transovarial transmission may take place
Animal-Arthropod-Man Cycle
Japanese encephalitis
The reservoir is in an animal,The virus is maintained in nature in a
transmission cycle involving the arthropod vector and animal
Man becomes infected incidentally
登革病毒 Dengue Virus
Dengue is the biggest arbovirus problem in
the world today with over 2 million cases per
year
Dengue is found in Southeast Asia,Africa
and the Caribbean and S America
Distribution of Dengue
病毒性状
黄病毒
55nm,+ssRNA,有包膜
4个血清型，有交叉反应传播环节
Transmitted by Aedes mosquitoes（ 伊蚊 ）
which reside in water-filled containers
Human infections arise from a human-
mosquitoe-human cycle
临床特点
隐性感染率高
登革热
高热，淋巴结肿大，肌肉酸痛，骨关节痛疼，头痛
，斑丘疹
登革出血热、登革休克综合症
在 再次感染患者 中，少数发展成严重的登革出血热
（ Dengue haemorrhagic fever ）和登革休克综合症（ Dengue shock syndrome ），死亡率达 5-10%
发病机机制与机体存在的抗体参与的 免疫病理反应有关诊断与预防
Diagnosis is made by serology
No specific antiviral therapy is available
Prevention of dengue in endemic areas depends on
mosquito eradication,The population should remove
all containers from their premises which may serve as
vessels for egg deposition
A live attenuated vaccine is being tried in Thailand
with encouraging results
流行性乙型脑炎病毒
Epidemic Type B Encephalitis
Virus first discovered and originally restricted to
Japan (1934),also called Japanese B
encephalitits virus
Now large scale epidemics occur in China,
India and other parts of Asia.
病毒性状
Belongs to Flavivirus
Typical arbovirus particle,20~30nm spherical
+ssRNA genome
Envelop with hemoagglutinin that can
agglutinate RBCs of chicken and pigeon
Only one serotype,can be controlled by
vaccine strategy
致病性
Transmitted by culex mosquitoes（库蚊）,
Since Culex has a flight range of 20km,all
local control measures will fail
The virus is maintained in nature in a
transmission cycle involving mosquitoes,birds
and pigs
Viruses are preserved in the body and egg of
mosquitoes,therefore,mosquitoes are the
long-term reservoir（蚊是储存宿主）
人被带毒的蚊虫叮咬后,绝大多数表现为隐性感染或仅轻微症状 。只有少数发生脑炎。
病毒侵入人体，经 两次病毒血症 后，播散到全身,10天左右潜伏期，出现发热、寒战及全身症状。 0.1%的患者 病毒越过血脑屏障进入脑组织，造成脑实质炎症和脑膜病变，临床表现为突然高热、头痛、呕吐、惊厥、昏迷等脑膜刺激症状和脑炎症状。 死亡率高达 10%—30%
部分患者恢复后留下精神障碍、运动障碍等后遗症
Laboratory Diagnosis
Serology
Virus isolation
RT-PCR
血清学诊断
血凝抑制试验 Hemoagglutinin Inhibition Test
Screening IgM-HI antibody for early diagnosis,75%
positive in acute patients
If the titer of HI test dropped 4 times after treated
with 2-mercaptoethanol,always means IgM positive
补体结合试验 Complement fixation test
Double serum samples,the titer of the second,the
first >4
The CF antibody of this virus can last only 2 to 4
months,so positive means newly infection
病毒分离 Virus isolation
Viremia lasts a very short period,it is hard to
isolate virus from blood.
Normally,the cerebral spinal fluid and brain
tissue are inoculated into suckling mice brain
预防 Prevention
Control and kill of mosquitoes
Pesticides,elimination of breeding grounds,insect
repellants
Prevent animal infection
Vaccination of pigs before the epidemic season
Vaccination
Children under 10-year-old,one month before the
epidemic season
Inactivated vaccine（灭活疫苗）,double
subcutaneous injections in duration of one week,
repeat vaccination one year later
Tick-borne encephalitis virus
蜱传脑炎病毒
森林脑炎病毒（ Forest Encephalitis Virus）
俄罗斯春夏脑炎病毒（ Russian Spring-
Summer Encephalitis Virus）
Morphology
Typically Flavivirus
Transmitted by tick
Can be found in Russia,Middle Europe,
and Germany,Epidemic infection also
occurs in northeastern China,Tick is the
host and transmitted vector,Cause
encephalitis
Diagnosis = JBV
Prevention
Prevent tick-biting is the key procedure
Inactivated virus vaccine is available
黄 病 毒
Department of Microbiology,HMU
第 33章黄病毒、出血热病毒、狂犬病病毒问题：
什么是虫媒病毒？常见的昆虫媒介有哪些？
登革病毒的所致疾病及传播方式
流行性乙型脑炎病毒的传播环节，如何控制？
引起肾综合征出血热的病毒是什么？自然宿主是什么？如何传染给人？
狂犬病病毒的致病机制、预防原则人畜共患病毒性疾病
Viral Zoonosis
人畜共患病
脊椎动物（ vertebrate animals）所患疾病能通过昆虫媒介直接或间接传递给人类
如果有昆虫参与，这个疾病也称为虫媒疾病
（ arboviral）
如狂犬病、肾综合症出血热、流行性乙型脑炎和埃博拉出血热虫媒病毒（ Arthropod-borne viruses
,arboviruses）是通过节肢动物（
arthropod vectors）传播的病毒
The WHO definition is as follows
Viruses maintained in nature principally,
or to an important extent,through
biological transmission between
susceptible vertebrate hosts by
haematophagus arthropods or
through transovarian and possibly
venereal transmission in arthropods
虫媒病毒种类
虫媒病毒分属 3个病毒科：
Togaviruses （ 披膜病毒科 ）
EEE,WEE,and VEE
Bunyaviruses （ 布尼亚病毒科 ）
Haemorrhagic Fever
Sandfly Fever,Rift Valley Fever,Crimean-Congo
Flaviviruses （ 黄病毒科 ）
Yellow Fever,dengue,Japanese Encephalitis
在我国流行并经病毒分离证实的虫媒病有
6种
流行性乙型脑炎
森林脑炎
登革热
基孔贡亚热
肾综合征出血热
新疆出血热黄病毒 Flaviviruses
登革病毒 Dengue viruses
流行性乙型脑炎病毒 Epidemic type B
encephalitis virus
蜱传脑炎病毒 Tick-borne encephalitis virus
黄病毒生物学特性
球形,20~60nm，个别达 100nm，有包膜,+ssRNA基因组，有感染性，只有一个读码框，编码一个大前体蛋白，切割后分成结构和调节蛋白
核心由 C蛋白和 RNA构成二十面体立称 核衣壳,包膜上有病毒编码的 M和 E蛋白,其中 E蛋白具有血凝素作用,
能凝集鸡红细胞
对酸、醚,氯仿敏感
在 节肢动物体 内增殖，对节肢动物不致病，但通过叮咬传染给脊椎动物和人类，引起 自然疫源性的人畜共患疾病,脑炎、黄热病和出血热等
致病呈明显的季节性和地区性节肢动物媒介
Arthropod Vectors
Mosquitoes （ 蚊 ）
Japanese encephalitis,dengue,yellow fever,St,
Louis encephalitis,etc.
Ticks （ 虱,蜱 ）
Crimean-Congo haemorrhagic fever,various tick-
borne encephalitis etc.
Sandflies （ 白蛉 ）
Sicilian sandfly fever,Rift valley fever.
Arthropod Vectors
Aedes Aegyti （ 伊蚊 ） Assorted Ticks （ 虱、蜱 ）
Phlebotmine Sandfly （ 吸血白蛉 ）Culex Mosquito （ 库蚊 ）
动物宿主（ Reservoirs）
In many cases,the actual reservoir is not known,The
following animals are implicated as reservoirs
鸟
Japanese encephalitis,St Louis encephalitis
猪
Japanese encephalitis
猴
Yellow Fever
啮齿类动物
Russian Spring-Summer encephalitis
传播环节
人 – 节肢动物 – 人
Dengue
动物 – 节肢动物 – 人
Japanese Encephalitis
混合方式：两种都有
some arboviruses such as yellow fever
Man-Arthropod-Man Cycle
Dengue
Reservoir may be in either man or arthropod vector
In the latter transovarial transmission may take place
Animal-Arthropod-Man Cycle
Japanese encephalitis
The reservoir is in an animal,The virus is maintained in nature in a
transmission cycle involving the arthropod vector and animal
Man becomes infected incidentally
登革病毒 Dengue Virus
Dengue is the biggest arbovirus problem in
the world today with over 2 million cases per
year
Dengue is found in Southeast Asia,Africa
and the Caribbean and S America
Distribution of Dengue
病毒性状
黄病毒
55nm,+ssRNA,有包膜
4个血清型，有交叉反应传播环节
Transmitted by Aedes mosquitoes（ 伊蚊 ）
which reside in water-filled containers
Human infections arise from a human-
mosquitoe-human cycle
临床特点
隐性感染率高
登革热
高热，淋巴结肿大，肌肉酸痛，骨关节痛疼，头痛
，斑丘疹
登革出血热、登革休克综合症
在 再次感染患者 中，少数发展成严重的登革出血热
（ Dengue haemorrhagic fever ）和登革休克综合症（ Dengue shock syndrome ），死亡率达 5-10%
发病机机制与机体存在的抗体参与的 免疫病理反应有关诊断与预防
Diagnosis is made by serology
No specific antiviral therapy is available
Prevention of dengue in endemic areas depends on
mosquito eradication,The population should remove
all containers from their premises which may serve as
vessels for egg deposition
A live attenuated vaccine is being tried in Thailand
with encouraging results
流行性乙型脑炎病毒
Epidemic Type B Encephalitis
Virus first discovered and originally restricted to
Japan (1934),also called Japanese B
encephalitits virus
Now large scale epidemics occur in China,
India and other parts of Asia.
病毒性状
Belongs to Flavivirus
Typical arbovirus particle,20~30nm spherical
+ssRNA genome
Envelop with hemoagglutinin that can
agglutinate RBCs of chicken and pigeon
Only one serotype,can be controlled by
vaccine strategy
致病性
Transmitted by culex mosquitoes（库蚊）,
Since Culex has a flight range of 20km,all
local control measures will fail
The virus is maintained in nature in a
transmission cycle involving mosquitoes,birds
and pigs
Viruses are preserved in the body and egg of
mosquitoes,therefore,mosquitoes are the
long-term reservoir（蚊是储存宿主）
人被带毒的蚊虫叮咬后,绝大多数表现为隐性感染或仅轻微症状 。只有少数发生脑炎。
病毒侵入人体，经 两次病毒血症 后，播散到全身,10天左右潜伏期，出现发热、寒战及全身症状。 0.1%的患者 病毒越过血脑屏障进入脑组织，造成脑实质炎症和脑膜病变，临床表现为突然高热、头痛、呕吐、惊厥、昏迷等脑膜刺激症状和脑炎症状。 死亡率高达 10%—30%
部分患者恢复后留下精神障碍、运动障碍等后遗症
Laboratory Diagnosis
Serology
Virus isolation
RT-PCR
血清学诊断
血凝抑制试验 Hemoagglutinin Inhibition Test
Screening IgM-HI antibody for early diagnosis,75%
positive in acute patients
If the titer of HI test dropped 4 times after treated
with 2-mercaptoethanol,always means IgM positive
补体结合试验 Complement fixation test
Double serum samples,the titer of the second,the
first >4
The CF antibody of this virus can last only 2 to 4
months,so positive means newly infection
病毒分离 Virus isolation
Viremia lasts a very short period,it is hard to
isolate virus from blood.
Normally,the cerebral spinal fluid and brain
tissue are inoculated into suckling mice brain
预防 Prevention
Control and kill of mosquitoes
Pesticides,elimination of breeding grounds,insect
repellants
Prevent animal infection
Vaccination of pigs before the epidemic season
Vaccination
Children under 10-year-old,one month before the
epidemic season
Inactivated vaccine（灭活疫苗）,double
subcutaneous injections in duration of one week,
repeat vaccination one year later
Tick-borne encephalitis virus
蜱传脑炎病毒
森林脑炎病毒（ Forest Encephalitis Virus）
俄罗斯春夏脑炎病毒（ Russian Spring-
Summer Encephalitis Virus）
Morphology
Typically Flavivirus
Transmitted by tick
Can be found in Russia,Middle Europe,
and Germany,Epidemic infection also
occurs in northeastern China,Tick is the
host and transmitted vector,Cause
encephalitis
Diagnosis = JBV
Prevention
Prevent tick-biting is the key procedure
Inactivated virus vaccine is available
