Rabies Virus在线视频

Hello, see you again.
大家好，我们又见面了

I’m Yun Su,
我是来自

from the Department of Microbiology
汕头大学医学院微生物学与

and Immunology,
免疫学教研室的

Shantou University Medical College.
苏芸老师

In this chapter,
这一章节

we will discuss about rabies virus
我们要学习一种能够导致

which causes a classic
人畜共患病的病原体

zoonotic infection.
狂犬病病毒

Here are learning objectives.
以下是这次课的学习目标

1.Describe the biological
1.描述狂犬病病毒的

properties of rabies virus;
生物学性状

2.Describe the epidemiology,
2.描述狂犬病的流行病学特点

explain the pathogenesis
解释狂犬病的致病机制

and the clinical course of rabies;
与临床病程

3.List the appropriate lab tests
3. 列举恰当的实验室

for diagnosis,
诊断方法

and know how to manage,
懂得如何预防

prevent,
处理

and control rabies viral infection.
及控制狂犬病病毒的感染

Let’s start with a case:
我们先来看一个病例：

A bat was found in
在一4岁男孩的房间里

a 4-year boy's bedroom.
出现了一只蝙蝠

It was there flying around all night.
蝙蝠在房间里飞了一整夜

The child was not bitten
孩子没有被咬伤

nor had any contact
也没有和蝙蝠

with the bat.
有任何接触

Four weeks later,
四周后

the boy developed a change
这个男孩发生了

in behavior,
行为改变

becoming irritable and agitated.
变得易怒与焦虑

Soon after,
不久后

he became confused with
男孩开始出现异常

uncontrollable thrashing about,
失控的吵闹行为

and inability to
大小便失控

handle his secretions.
流涎

He became comatose
之后男孩陷入昏迷

and eventually died
最终因

from respiratory arrest.
呼吸骤停死亡

What did the child have?
这个男孩到底得了什么病？

It was rabies!
狂犬病!

What kind of disease is rabies?
狂犬病是一种怎样的疾病呢？

Rabies is an acute
狂犬病是一种

and fatal infection of
由狂犬病病毒引起的

the central nervous system,
急性，致死性

caused by rabies virus.
中枢神经系统感染疾病

Now,
现在

we will focus on the
我们来学习狂犬病的

causative agent——rabies virus.
病原体--狂犬病病毒

What are the biological
狂犬病病毒有什么

properties of rabies virus?
生物学特性？

Rabies virus
狂犬病病毒

is the most important pathogen
是弹状病毒科中

of the rhabdoviruses.
最重要的成员

As you can see in the picture,
如图所示

the virions appear as bullet-
病毒体外观呈

shaped particles.
子弹状

The particles are surrounded
病毒颗粒最外层

by an envelope,
是包膜

covered with protruding spikes.
包膜上覆盖着刺突

The spikes are composed
刺突是

of the viral glycoprotein--
吸附蛋白

the attachment protein.
由糖蛋白构成

It can bind to AChR,
吸附蛋白可与AChR

NCAM(neural cell adhesion molecules),
NCAM（神经细胞粘附分子）

or other molecules
以及其他

in the peripheral nervous system,
外周神经受体分子结合

and stimulate the host immune system
也可刺激免疫系统

to generate neutralizing antibodies.
产生中和抗体

Inside the envelope
包膜内部

is a ribonucleocapsid.
是核衣壳

The helical nucleocapsid
核衣壳

is coiled
为螺旋

symmetrically into
对称结构

a cylindrical structure,
呈圆柱状

which encloses single-stranded,
里面是

negative-sense RNA genome.
单负链RNA基因组

The genome encodes five proteins:
基因组编码5种病毒蛋白包括

nucleoprotein(N),
核蛋白（N)

phosphoprotein(P),
磷蛋白(P)

large polymerase protein(L),
大多聚酶蛋白（L)

matrix protein(M),
基质蛋白(M)

and glycoprotein(G).
和糖蛋白（G)

The viral ribonucleoprotein (RNP) core
病毒RNA

consists of the viral RNA
是核糖核蛋白（RNP）的核心

encapsulated by N protein
它被N蛋白包绕

and associated with P and L protein.
同时结合于P蛋白和L蛋白

How does the rabies virus
狂犬病病毒是如何

cause the disease?
致病的？

Let’s turn to the pathogenesis
我们来学习狂犬病病毒的

of the rabies virus.
致病机制

Rabies infection is usually
狂犬病主要由

from the bite of a rabid animal.
带毒的动物咬伤所致

The pathogenesis of rabies infection
其致病机制经历了

includes a sequence of events.
一系列过程包括

1.The virus is inoculated by the bite.
1.病毒通过伤口侵入

2.Virus replicates in muscle tissue.
2.病毒侵入后在伤口局部肌肉组织中复制

3.Virus binds to AChR
3.在神经肌肉交界处

at neuromuscular junction.
病毒与AChR结合

4.Virus travels along axons
4.进而沿着神经轴突

in peripheral nerves
快速逆行并

via fast retrograde transport.
在周围神经组织传播

5.Virus replicates
5.病毒在局部

in the local dorsal root ganglia.
背根神经节大量复制

6.Virus rapidly ascends along
6.并且沿着脊髓迅速上行

the spinal cord.
侵入中枢神经系统

7.Virus infects the brain rapidly.
7.之后，病毒迅速感染大脑

The neurons in the infected areas
感染部位的神经元发生

degenerate and lose their functions.
退行性变并出现功能异常

8.Virus spreads along the nerves
8最后病毒沿着传出神经到达

to the eyes,
眼睛

salivary glands,
唾液腺

skin,
皮肤

and other organs.
以及其他的器官

The disease is an acute,
狂犬病是一种急性

fulminant,
暴发性

fatal encephalitis.
致死性脑炎

A typical course is divided into
典型的狂犬病病程分为

3 stages.
3个阶段

1.Incubation period,
1.潜伏期

2.Prodromal phase,
2.前驱期

3.Neurologic phase.
3.神经症状期

The incubation period in humans
狂犬病的潜伏期

is typically 1–3 months
通常是1-3个月

but may be as short as 2 days
但也可能短至2天

or as long as 1 years.
或者长达1年

The length of the incubation phase
潜伏期的长短

is determined by
取决于

1.the distance between site of the bite
1.咬伤部位与

and CNS,
CNS的距离

2.size of the inoculum,
2.入侵病毒的量

3.age of host,
3.宿主的年龄

4.immune status of host,
4.宿主的免疫力

5. viral strain involved.
5.病毒株的类型

In this incubation period,
潜伏期期间

the virus replicates
病毒在

in the muscle at the site of the bite,
咬伤局部的肌肉中复制

the patient has few
患者仅有轻微症状

or no symptoms.
或没有症状

After weeks to months,
数周到数月后

the patient enters prodromal phase.
患者进入前驱期

During the prodrome
在前驱期期间

(lasting 2–10 days),
（一般持续2-10天）

the patient may show any of
患者出现

the following nonspecific symptoms:
一些非特异性症状

fever,
发热

malaise,
萎靡不振

headache,
头痛

pain
疼痛

or numbness at the site of the bite,
或咬伤部位麻木

fear of light,
畏光

nausea and vomiting, etc.
恶心和呕吐等

What will happen next？
接下来会发生什么？

Infection of the brain causes classic
大脑感染会导致患者出现典型的

symptoms (neurologic phase).
神经症状（神经症状期）

Patients show signs of nervous system
患者出现神经功能障碍

dysfunction such as anxiety,
如焦虑

disorientation,
定向障碍

hallucinations,
幻觉

and bizarre behavior.
和怪异行为

Besides,
此外

general sympathetic
还会出现交感神经

over-activity is evident,
过度兴奋的表现

including increased tears,
包括流泪

sweat and saliva production,
流汗和流涎

and so on.
等等

Hydrophobia (fear of water),
恐水（怕水）

is the most characteristic symptom.
是狂犬病最典型的症状

Neurologic phase
神经症状期之后

is followed by convulsive seizures
患者可能出现惊厥

or coma and death.
或昏迷、猝死

The major cause of death
患者死亡的主因

are neurologic complications
是神经系统并发症

and cardiorespiratory arrest.
和心肺骤停

Rabies is fatal
狂犬病一旦

once clinical manifestations
出现明显临床表现

become apparent.
往往致死

Recovery and survival
康复和存活者

are extremely rare.
非常罕见

Rabies infection
狂犬病病毒感染

does not elicit
通常

an antibody response
在疾病后期

until the late stage of the disease.
才诱导抗体反应

Administration of antibody
如果足够早地使用抗体

can stop disease
能阻止

progression only if given early enough.
疾病的进展

The table here
这个表格

summarizes the progression of
总结了狂犬病病程

rabies disease.
的3个阶段

We can review the 3-stage course.
我们可以用来复习

At each stage,
每一个阶段中

there are various manifestations
因为病毒感染状态

with different virus states
和机体免疫反应的不同

and immunological responses.
患者可出现不同的临床表现

In this session,
接下来

we will draw your attention
我们将学习

to the epidemiology.
狂犬病的流行病学特点

Rabies is the classic zoonotic infection
狂犬病是典型的人畜共患病

transmitted from animals to humans.
可由动物传播给人类

The disease
这种疾病

has a widely distributed animal
有广泛的

reservoir as you can imagine:
动物宿主

wild animals and unvaccinated dogs
包括野生动物与未免疫接种的犬类

and cats.
和猫类

In rural regions,
在农村地区

many species of wildlife
多种野生动物

can serve as transmitters,
都可以成为传染源

and in urban areas,
在城市

dogs are the main offenders.
犬类是主要的传染源

There are two principal sources
病毒有两个重要的

of viruses:
来源

1.major source:
1.主要来源

from saliva of an infected animal;
来自受感染动物的唾液

2.minor source:
2.次要来源

from aerosol in an enclosed
来自被带毒蝙蝠污染

environment containing rabid bats.
的密闭环境中的气溶胶

How can an individual become infected?
人是怎么被感染的？

The routes can be from
传播途径包括

1.the bite of a rabid animal;
1.被患狂犬病的动物咬伤

2.scratches, abrasions,
2.被感染动物抓伤、擦伤

or open wounds
或开放性伤口

that come into contact
接触了

with saliva or other infectious material
被感染动物的唾液

from a rabid animal;
或其他被病毒污染的物品

3.inhalation of aerosolized virus;
3.吸入了带有病毒的气溶胶

4.corneal and organ transplants.
4.移植了被病毒污染的角膜或其他器官

Who are at risk of rabies infection?
哪些人有感染狂犬病的风险？

1.Veterinarians and animal handlers;
1.兽医和动物饲养员

2.Persons bitten by a rabid animal;
2.被患病动物咬伤的个体

3.Inhabitants of countries with no pet
3.无宠物免疫接种计划

vaccination program.
国家的居民

General speaking,
一般来说

a person with a history of an animal bite
人如果有动物咬伤史

and presents with neurologic symptoms
且出现神经系统症状

establishes the diagnosis of rabies.
可初步诊断狂犬病

Laboratory tests are usually performed
实验室检测通常

to confirm or exclude
用于确诊或排除

the diagnosis an individual or animal.
个人或动物患病

Initially,
首先

we should collect proper specimens
我们需要收集合适的标本

such as saliva,
如唾液

serum,
血清

cerebrospinal fluid,
脑脊液

brain tissue,
脑组织

neck skin biopsy,
颈部皮肤活检组织

autopsy material,
尸检材料

and impression smears of the cornea.
或者角膜印片

Then,
之后

several tests could be performed.
可进行以下几种实验室检查

1.Detection of Negri bodies.
1.检测内基小体

Negri bodies——
内基小体

intracytoplasmic inclusions can
是一种存在于胞浆中的包涵体

often be identified in infected cells.
常在被感染的细胞中出现

2.Antigen and genome detection.
2.检测抗原及基因组

Currently,
目前

antigen detection using
抗原检测

DFA(direct immunofluorescence assay),
常采用DFA（直接免疫荧光法）

or genome detection using RT-PCR
病毒基因组检测采用RT-PCR法

are relatively quick
这些都是比较快速

and sensitive methods
敏感的

for diagnosing rabies.
诊断方法

3.Antibody detection.
3.抗体检测

Antibodies to rabies
检测狂犬病病毒抗体

can be demonstrated,
可作为辅助诊断

and sometimes viral isolation
有时也可以进行

can be also performed.
病毒分离

Clinical rabies is almost always fatal.
有临床症状的狂犬病几乎都是致命的

How do we deal with rabies infection?
我们要如何处理狂犬病？

Actually,
实际上

once the symptoms have appeared,
狂犬病一旦出现症状

there is no treatment
无有效的治疗方法

and only supportive care can be given.
只能进行支持性治疗

So,
所以

preventive measures are of paramount
预防措施对于

importance to stop the disease.
阻止狂犬病的发生至关重要

1.The first measure
1.预防的第一步是

is local treatment of the wound.
处理局部伤口

The wound should be washed
应立即用肥皂和水

immediately with soap
或消毒剂

and water or disinfectant.
充分清洗伤口

Human rabies immunoglobulin (HRIG)
同时在伤口周围注射

can be injected near the wound.
人类狂犬病免疫球蛋白（HRIG)

2.Subsequently,
2.接下来

four immunizations with rabies vaccine
在4周内完成

are administered over 4 weeks.
4次狂犬病疫苗的接种

This might be the only hope
这可能是

for preventing overt
防止感染者出现

clinical illness in the affected person.
明显临床表现的的唯一希望

3.For the people at high risk,
3.高危人群

pre-exposure prophylaxis with vaccine
可进行暴露前预防接种

can reduce the odds of infection.
这可减少感染的机会

Ultimately,
最后

effective control of rabies
家养动物

in domestic
和野生动物

and wild animals is essential for
狂犬病的有效控制是

prevention of human rabies.
预防人类狂犬病的首要措施

The control depends on management of
狂犬病的有效控制还取决于全社会对

stray and unwanted animals,
流浪和遗弃动物的监管与处理

and vaccination program
以及犬类、猫类免疫接种

for all dogs and cats.
计划的广泛开展

Lastly, let’s return to the case.
我们重新回顾一下这个病例

What did the child have?
病例中的孩子得了什么病？

What is rabies?
什么是狂犬病？

Hope you have got the answer.
希望大家已经有了答案

Thank you for your attention!
谢谢大家的聆听

See you soon.
下次再见