MICROBIOLOGY PPT LECTURE NOTES | Karya Tulis Ilmiah
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
Prevalence in China
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
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）
Culex Mosquito （库蚊）
Assorted Ticks （蜱）
Phlebotmine Sandfly （吸血白蛉）
动物宿主（ Reservoirs ）
In many cases, the actual reservoir is not known. The
following animals are implicated as reservoirs
鸟
猪
– Japanese encephalitis, St Louis encephalitis
猴
– Japanese encephalitis
– 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 humanmosquitoe-human
reservoir: monkey and human beings
occur in both an urban and jungle cycle
隐性感染率高
临床特点
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 longterm 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 SpringSummer 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
Prevalence in China
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
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）
Culex Mosquito （库蚊）
Assorted Ticks （蜱）
Phlebotmine Sandfly （吸血白蛉）
动物宿主（ Reservoirs ）
In many cases, the actual reservoir is not known. The
following animals are implicated as reservoirs
鸟
猪
– Japanese encephalitis, St Louis encephalitis
猴
– Japanese encephalitis
– 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 humanmosquitoe-human
reservoir: monkey and human beings
occur in both an urban and jungle cycle
隐性感染率高
临床特点
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 longterm 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 SpringSummer 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