VirologyVirology病 毒 学病 毒 学

Conception Virology is a subject for study of viral structure,

physical and chemical properties, the relationship between viruses and hosts, diseases caused by viruses.

Virology is the study of viruses, complexes of nucleic acids and proteins that have the capacity for replication in animal, plant and bacterial cells .

Viruses come in two basic types※ , those that have a genome of DNA and those that have a genome of RNA.

Chapter 18Chapter 18

General properties of virusGeneral properties of virus病毒的基本性状病毒的基本性状

※ This chapter will focus on Conceptions virus, virion 病毒体 , capsid 衣壳 , nucleocapsid 核衣壳 ,

naked virus 裸露病毒 , enveloped virus 包膜病毒 , viral replication 病毒复制 , defective viruses 缺陷病毒 ,

abortive infection 顿挫感染， interference 病毒的干扰现象 Questions

Describe the structures of viruses. List the steps in normal viral replication What is viral interference and its application? Compare viruses with bacteria. Describe the distinctive features of virus.

What is virus ? ※Viruses

the smallest infectious and acellular microbe consisting only one kind of nucleic acid (DNA or RNA), and which obligately 严格地 replicate inside host cells.

※ Virions 病毒体 The complete mature infectious viral particle, it is the extracellular structure of virus.

※ Distinctive features 特性： Acellular microbes 非细胞型 Small enough to pass through 0.

2μm filters 过滤器 and can retain infectivity

Obligatory intracellular parasites 严格细胞内寄生

Contain DNA or RNA Self-replication Nonsensitive to antibiotics

Differentiation of viruses from bacteria

  Virus Bacterium

Size 0.02 ～ 0.3um 0.5 ～ 3.0um

Structure Acellular microorganism

Prokaryotic microorganism

Nucleic acid DNA or RNA DNA and RNA

Growth on cell free medium

Cannot grow Can grow

Mode of multiplication Replication Binary fission

Ribosome 核糖体 None Has ribosome

Antibiotic Resistant Sensitive

Interferon 干扰素 Sensitive Resistant

I. Size, shape and structureI. Size, shape and structure

A.A. Size:Size: The unit of measurement The unit of measurement ? ? nmnm ( nanometer( nanometer 毫微米 毫微米 , , 纳米纳米 1/1000u1/1000umm 微米 微米 ))

Parvoviruses细小病毒

poxviruses 痘病毒

1. Staphylococcus aureus1. Staphylococcus aureus 2. Rickettsia2. Rickettsia 立克次体立克次体 3. Chlamydia3. Chlamydia 衣原体衣原体 4. Poxviruses4. Poxviruses 痘病毒痘病毒 5. Bacteriophage of E. coli5. Bacteriophage of E. coli 6. Influenza virus6. Influenza virus 流感病毒流感病毒 7. Adenovirus7. Adenovirus 腺病毒腺病毒 8. Encephalitis B virus8. Encephalitis B virus

乙脑病毒乙脑病毒 9. Poliovirus9. Poliovirus

脊髓灰质炎病毒脊髓灰质炎病毒

Comparative sizes of virions and bacteriaComparative sizes of virions and bacteria

B. Shape: round, rod, filamentous, tadpole 蝌蚪 , bullet 子弹 , brick 砖 , etc

Tobacco mosaic virus 烟草花叶病毒 :

rod-shaped

HIV人类免疫缺

损病毒Spherical

VSV: bullet-shaped 子弹(Vesicular stomatitis 水泡性口炎 virus):

Bacteriophage T4: tadpole-shaped 蝌蚪

Ebola Virus: filamentous shape

※Basic structure 基本结构 : Core 核心 : Viral nucleic acid

(DNA or RNA) Capsid 衣壳 : Protein shell

Capsomers 壳粒 (morphological subunit) polypeptide molecules (c

hemical subunit)Core + Capsid → nucleocapsid

核衣壳 Envelope 包膜：

Spike 刺突

C. Structure:

It is decided by arrangement of capsomers. 壳粒

Helical symmetry 螺旋对称 (e.g., tobacco mosaic virus)

Icosahedral symmetry二十面体立体对称

(e.g., adenovirus) complex symmetry 复合对称

(e.g., Poxviruses ) 作用：保护、鉴定、分类、 介导、免疫原性

D. Symmetry of viral nucleocapsids ※ 核衣壳的对称型

Naked virus 裸露病毒 : Nucleocapsid is the virion.

Enveloped virus 包膜病毒 : Nucleocapsid+Envelope→virion spikes or peplomers 包膜子粒 ;

Special structure 特殊结构 :

e.g. Retrovirus has reverse transcriptase 逆转录酶

※ Conceptions

nucleocapsid

HA - hemagglutinin

lipid bilayer envelope

NA - neuraminidase

结构举例 : Influenza virus 流感病毒

CHEMICAL COMPOSITION OF VIRUSECHEMICAL COMPOSITION OF VIRUSESS 病毒的化学组成病毒的化学组成

A. Viral ProteinA. Viral Protein 1. The structural proteins of viruses1. The structural proteins of viruses 2. The non-structure proteins2. The non-structure proteins 非结构蛋白非结构蛋白

B. Viral Nucleic AcidB. Viral Nucleic Acid C. Viral EnvelopesC. Viral Envelopes D. Viral GlycoproteinsD. Viral Glycoproteins: are virus-encoded : are virus-encoded

In host cell, virus replicates its nucleic acid and synthesizes its proteins, then assembles 装配 them to form progeny viral particles 子代病毒颗粒 that are released mainly by budding or host cell lysis.

II. Replication 病毒的复制

Absorption /Attachment

Penetration 穿入 Uncoating 脱壳 Biosynthesis 生物合成 Assembly 组装

Maturation and Release

A. ※ Normal Replication 正常复制

1 、 Attachment / Absorption 吸附

Mechanisms:

A. Endocytosis 内吞作用 The naked viruses 裸露病毒B. Fusion 融合 between cell membrane and viral envelope The enveloped viruses 包膜病毒

2 、 Penetration 穿入 : the internalization 内在化 of virus into the host cell

C. Nucleic acid translocation 移动 : Some bacteriophages and naked viruses

3 、 Uncoating 脱壳 : capsid 衣壳 is removed and viral nucleic acid is released in the host cell.

4 、 Biosynthesis 生物合成 : Biosynthesis includes:

Viral genome replication 基因复制 Viral protein synthesis 蛋白质合成 Eclipse phase 隐蔽期 : the viral particles can not be found inside host cell and the viruses seem to have disappeared.

Replication of dsDNA viruses: e.g., Herpes simplex virus 单纯疱疹病毒

double-strand DNA

(template)

Cell’s DNA-dependent RNA polymerase early mRNA

translation DNA-dependent DNA polymerase

semi-conservative replication 半保留复制

progeny 子代 viral DNA late mRNA late proteins transcription translation

Transcription 转录

early proteins(nonstructural proteins)

(structural proteins)

progeny viral nucleocapsid 子代病毒核衣壳assembly 组装

5 、 Assembly 组装 : capsid + viral genome → nucleocapsid

Site: a. DNA viruses (except poxvirus): cell nucleus 细胞核 ;

b. RNA viruses and poxvirus: cell cytoplasm 细胞质 ; Manner: a. assemble an empty shell (procapsid 前 衣 壳 ), then viral genome fill in.

Enveloped virus: nucleocapsid + envelope 包膜 → virion

b. Viral capsomers 壳粒 array 排列 around the viral genome to form helical symmetry nucleocapsid.

Naked virus: nucleocapsid → virion

6 、 Maturation and Release 成熟与释放

The process of progeny viruses getting out of host cell.

Naked viruses: released after the host cells lysis 溶解 .Enveloped viruses: Usually released by budding 出芽 and acquire their envelope during budding. Traversal of cell-cell bridges 细胞间横桥 : e.g., defective measles virus 缺陷麻疹病毒 SSPE (Subacute sclerosing panencephalitis) 亚急性硬化性全脑炎

Host cell lysis Budding

复制的完整过程

1. Defective viruses 缺陷病毒 : are genetically deficient 遗传缺陷 and incapable of

producing infectious progeny virions 子代病毒体 .

Helper viruses 辅助病毒 : Viruses can supplement 补充 the genetic deficiency a

nd make defective viruses replicate progeny virions when they simultaneously 同时 infect host cell with defective viruses.

B. ※Abnormal replication 异常增殖 :

Defective Viruses 缺陷病毒 lack gene(s) necessary for a complete infectious cycle helper virus provides missing functions

A B

A B

example of defective virus AAV & adenovirus 腺病毒伴随病毒与腺病毒 HDV & HBV 丁肝病毒与乙肝病毒

DIP 缺陷干扰颗粒 : Defective viruses which can occupy the cell machinery

required for normal virus replication to prevent 防止 virus production, are called "defective interfering particles" (DIP).

缺陷病毒虽不能复制，但却具有干扰同种成熟病毒体进入细胞的作用，称缺陷干扰颗粒。

occur naturally and can cause disease

e.g., DI measles virus cause SSPE. (subacute sclerosing panencephalitis) 亚急性硬化性全脑炎

Defective interfering particles (DIP)

Virus infection which does not produce infectious progeny

because the host cell cannot provide the enzyme, energy or

materials required for the viral replication, is called abortive

infection. 因为宿主细胞不能提供酶类、能量和病毒复制的必要成分，导致病毒感染后不能产生感染性子代。

non-permissive cells 非容纳细胞 The host cells that can’t provide the conditions required for viral

replication. 不能提供病毒复制条件的细胞permissive cells 容纳细胞 The host cells that can provide the conditions required for viral replication.

能支持病毒完成正常增殖的细胞

2. Abortive infection※ 顿挫感染 :

※Viral interference When two viruses infect one cell at the same time 同时

or successively 先后 , the virus A may inhibit the replication of virus B, this phenomenon is called viral interference.

Range of interference occurrence between the different species of virus; 异种病毒 between the same species of virus; 同种病毒 between the inactivated and living viruses ; 灭活病毒与活病毒 between the defective virus and normal virus ; 缺陷病毒与正常病

毒

III. Viral interference 病毒的干扰现象

1. Virus A may inhibit virus B adsorption by blocking

防碍 or destroying 破坏 receptors on host cell;

2. Virus A may compete with virus B for replication materials; 竞争复制需要的物质

e.g., polymerase, translation initiation factors, etc.

3. Virus A may induce the infected cell to produce interferon 干扰素 that can prevent B viral replication.

Viral interference Mechanisms 干扰机制

Advantage a. Stop viral replication and lead to patients recovery.

阻止病毒复制，导致宿主康复 b. Inactivated virus or live attenuated virus can be used

as vaccine to interfere with the virulent viral infection.

灭活病毒和减毒活病毒作为疫苗干扰毒性病毒感染Disadvantage May decrease the function of vaccine 可能减低疫苗效果

Signification Viral interference 干扰意义

Physical factors: Temperature ：耐冷不耐热，

反复冰融可灭活， 保存应快速低温冷冻

pH ： 6~8 稳定，保存可用 50% 甘油缓冲盐水

radiation ： X 射线、 γ 射线、 紫外线

IV. physical & chemical effects on viruses 理化因素对病毒的影响

-196℃

IV. physical & chemical effects on viruses 理化因素对病毒的影响 Chemicals factors : Phenol 苯酚 ; Formaldehyde 甲醛 /formalin 福尔马林 ; 70% ethanol 乙醇 ; Oxidizing agents 氧化剂 ; Lipid solvents 脂溶剂 ;

Biological factors ： Antibiotic 利于病毒分离 , interferon 干扰素 , etc.