Flavivirus
Xiao-Kui GUO
Dept,of Microbiology and Parasitology
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
Prevalence in China
Scientist collecting specimens from trapped rodents
Common characteristics
? 40~70 nm in diameter,+ssRNA spherical
enveloped
? Hemophilic arthropods as vector,and viruses
replicate in arthropod
? 5 type clinical manifestations and diseases
related to season and district,
Major Clinical Categories of Arboviral
Disease
? No clinical illness,
? Febrile systemic illness,
? Encephalitis
? Haemorrhagic Fever,
? Hepatitis
? arthritis
Genome
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 （ 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 （ 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
Mature Dengue-2 virus particles replicating in
five day old tissue culture cells
传播环节
? Transmitted by Aedes mosquitoes（ 伊蚊 ）
which reside in water-filled containers
? Human infections arise from a human-
mosquitoe-human
? reservoir,monkey and human beings
? occur in both an urban and jungle 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
– ADE/immune enhancement
A large subcutaneous haemorrhage on the upper arm of a patient with
dengue haemorrhagic fever,
Lab Diagnosis
? Culture in C6/36 cells,1-3days
? HI,1 weeks
? CFT,
? ELISA,IgM ; IgG
5 days:80%
6-10 days, 99%
预防
? 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
Biological properties
? Small spherical enveloped virus
? SP,C; M; E(HA)
? Replicates in susceptible animals,embryo eggs
and cell culture;
? Stable antigenicity;
? Sensitive to lipid solvent agents,physical and
chemical treatments
Epidemiology
? Source of infection,Patients and infected
animals,e.g,young pigs
? it is mosquito borne
? Young Pigs and birds are its natural
hosts
?
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）
Aedes mosquito feeding
? 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
Pathogenicity and Immunity
? Virus reticular endothelial system
Viremia
Liver or Spleen
Viremia
CNS encephalitis
? Immunity,Long
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
? Incubation, 10-14 days
? Diagnosis = JBV
? Prevention
– Prevent tick-biting is the key procedure
– Inactivated virus vaccine is available
Xiao-Kui GUO
Dept,of Microbiology and Parasitology
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
Prevalence in China
Scientist collecting specimens from trapped rodents
Common characteristics
? 40~70 nm in diameter,+ssRNA spherical
enveloped
? Hemophilic arthropods as vector,and viruses
replicate in arthropod
? 5 type clinical manifestations and diseases
related to season and district,
Major Clinical Categories of Arboviral
Disease
? No clinical illness,
? Febrile systemic illness,
? Encephalitis
? Haemorrhagic Fever,
? Hepatitis
? arthritis
Genome
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 （ 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 （ 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
Mature Dengue-2 virus particles replicating in
five day old tissue culture cells
传播环节
? Transmitted by Aedes mosquitoes（ 伊蚊 ）
which reside in water-filled containers
? Human infections arise from a human-
mosquitoe-human
? reservoir,monkey and human beings
? occur in both an urban and jungle 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
– ADE/immune enhancement
A large subcutaneous haemorrhage on the upper arm of a patient with
dengue haemorrhagic fever,
Lab Diagnosis
? Culture in C6/36 cells,1-3days
? HI,1 weeks
? CFT,
? ELISA,IgM ; IgG
5 days:80%
6-10 days, 99%
预防
? 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
Biological properties
? Small spherical enveloped virus
? SP,C; M; E(HA)
? Replicates in susceptible animals,embryo eggs
and cell culture;
? Stable antigenicity;
? Sensitive to lipid solvent agents,physical and
chemical treatments
Epidemiology
? Source of infection,Patients and infected
animals,e.g,young pigs
? it is mosquito borne
? Young Pigs and birds are its natural
hosts
?
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）
Aedes mosquito feeding
? 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
Pathogenicity and Immunity
? Virus reticular endothelial system
Viremia
Liver or Spleen
Viremia
CNS encephalitis
? Immunity,Long
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
? Incubation, 10-14 days
? Diagnosis = JBV
? Prevention
– Prevent tick-biting is the key procedure
– Inactivated virus vaccine is available
