Download Chapter 3: Viruses 第三章：病毒

Chapter 3: Viruses 第三章：病毒 - 非细胞型生物的形态构造
Thai dogs carry bird-flu virus, but will they spread it?
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NATURE Vol 439: 773 (16 February 2006)
Vaccine? China!
Bacteriophage噬菌体 T4 & lambda
Of ancient origin
Avian Influenza H5N1 - No. 1 threaten to human
How H5N1 works?
What is Virus?
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Basically a form of genetic information insures continued survival
Reproduces DNA/RNA within living cells utilizing mechanisms of cells
Diagram of Five Kingdoms
Viruses are…
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Acellular 无细胞的
– Pass the bacteria-proof filter
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Obligate intracellular parasites专性细胞内寄生
– No ATP generating system
– No Ribosomes or Protein Synthesis
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Can be CRYSTALLIZED 结晶: life?
Filtration of a mixture of bacteria and viruses
Structure: Bacteria vs Virus
Major difference between virus & prokaryotes
Content
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Virus: morphology & replication真病毒形态构造和复制
Subvirus 亚病毒
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Virus and the application
Relative size of viruses & bacteria
Critical Thinking
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Do you think bacteria as small as viruses will ever be discovered?
Typical Structure of Virus
病毒的典型构造
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Viron (virus particle) 病毒颗粒
• Core 核心: nucleic Acid 核酸
– Capsid 衣壳: coat Protein
– Capsomer 衣壳亚基
– Structural/catalytic proteins
– Binding sites of antigen
– Envelope 包膜: some viruses
– Binding Sites (spike)
Naked or Enveloped Virus
裸露或包膜的病毒
Types of Viral Nucleic Acid
病毒核酸类型
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DNA or RNA: Never both
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Animal virus: linear dsDNA, ssRNA
Plant virus: ssRNA
Phage: linear dsDNA
Fungi virus: dsRNA
Algae virus: dsDNA
DNA viruses
When studying Adenovirus…
• One piece of DNA can pair with one piece of mRNA coming from different location 
Split gene
• Richard Roberts & Phillip Sharp shared 1993 Nobel Prize for the discovery of introns
RNA viruses: (-) and (ds)
Viral Morphology – Shape
病毒形态学:形状
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Symmetry 对称性
– Helical 螺旋形的
• Polyhedral 多面: Icosahedral 二十面体
• Complex 复合对称
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Enveloped
• Enveloped Helical, Polyhedral, Complex
Basic types of virus symmetry
Tobacco mosaic virus (TMV) 烟草花叶病毒-helical capsid
Adenovirus - icosahedral symmetry 腺病毒:二十面体对称
Complex symmetry 复合对称
“Colony Shape” 病毒群体形态
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Inclusion Body 包含体
– Polyhedron 多角体
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Plaque 噬菌斑:
– Clear zones on plate
Measurement of infective phages - Titer 效价
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Titer 效价:
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Number of infective phages/ml
pfu: plaque-forming unit 噬菌斑形成单位
Methods:
• Double-layered plate 双层平板法: used widely
• Single-layered plate 单层平板法
• Fast-slide method 玻片快速法
Measurement of titer 效价测定 Plaque Assay: double-layed
Host Range 宿主范围
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Most: narrow host range
– Polio virus 脊髓灰质炎病毒: nerve cells
– Adenovirus 腺病毒: upper Respiratory Tract 上呼吸道
• None can cross eukaryotic/prokaryotic boundary
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20+ virus family infecting man
Evolution of H5N1 & possible path to humans
Phage T4 replication: 5 steps T4噬菌体复制的五个步骤
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No growth
Adsorption 吸附
Penetration 侵入
Replication 复制
Assembly (Maturation) 装配(成熟)
Release 释放
Virus Replication
Penetration of T4
Eukaryotic virus: entry by Engulfment/endocytosis 胞饮作用
Eukaryotic virus entry by fusion with host CM 膜融合
Maturation and release of virus by budding 出芽
无包膜dsRNA病毒入侵机制
• 3.3 Å Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for
Cell Entry
• Cell, 141 (3), 472-482, 15 April 2010
• Xing Zhang, Lei Jin, Qin Fang, Wong H. Hui, Z. Hong Zhou
Replication Strategy of dsDNA Viruses
The Baltimore Classification Scheme
Life cycle of bacteriophage
噬菌体生活周期
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Lytic Cycle 裂解性生活周期
• Only multiply and kill cell
• Virulent phages 裂性噬菌体, e.g. T4
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Lysogenic Cycle 溶源性生活周期
• Either multiply via the lytic cycle or enter a quiescent state
• Temperate phages 温和性噬菌体, e.g. λ
Lytic Phage Multiplication Cycle
裂解性生活周期
Lysogenic Cycle 溶源性生活周期
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Integration 整合
– “Latent”
– Prophage 前噬菌体:
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Release
– Lysogenic/phage conversion 溶源转变
Termination of Lysogeny溶源终止
Retro Viruses 反转录病毒
• Many Cancer-causing viruses
• HIV
– AIDS: Acquired Immunodeficiency Syndrome
• Central Dogma
DNA -----> mRNA ----> Protein
• Retro Virus
RNA --> DNA-->mRNA--> Protein
How HIV attach cells?
华人科学家何大一首创“鸡尾酒疗法”
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HIV逆转录酶抑制剂
HIV蛋白酶抑制剂
免疫机能调节剂
抗感染
营养支持
Vaccine for HIV ?
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HIV mutates too rapidly
– Reverse Transcriptase 反转录酶: at least 1 mutation each time
• Asymptomatic 无症状: 1 million variants
• Advanced: 100 million variants
Merck AIDS Failure Hurts Global HIV Vaccine Research
- Merck's HIV vaccine steps out of development
• Science, 2007, Sep. 18
• Merck & Co. has stopped the Phase II trial of its V520 HIV vaccine after interim results
showed that the vaccine was not effective and did not prevent infection.
Viral Disease Treatment/Prevention
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No viral disease has ever been CURED by medical treatment.
Viruses are not susceptible to ANTIBIOTICS
Smallpox vaccine targeted to cancer?天花疫苗瞄准癌症
肝脏肿瘤用转基因病毒治疗前（上）及治疗4周后（下）
• 《临床研究》： 2007-11-2
2009年12月4日《科学》：有望针对丙型肝炎的新型抗病毒药
Subvirus 亚病毒
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Viroid 类病毒
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Circular RNA without protein wrapping
Smallest molecular organism
Potato spindle tuber disease (PSTD)
Virusoids (viroid-like) 类类病毒
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Wrapped in plant virus (e.g. tobacco)
ssRNA
Prion 朊病毒 (protein infection)
Viroid-infected plants can be symptomless or develop symptoms that range from mild
to lethal, depending on the viroid
Virus and Application
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Industrial/Economic: 工业
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Medical 医学
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Recombinant DNA vectors 重组DNA
– Bacteriophage and fermentation
– Insect virus and biocontrol
– Phage typing (e.g. Staphylococcus)
Key Words
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Viron 病毒粒子
Capsid 衣壳
Envelope 包膜
Nucleocapsid核衣壳
Inclusion body包含体
Plaque 噬菌斑
Lytic Cycle
Virulent phages 烈性噬菌体
Lysogenic cycle
Temperate phages温和噬菌体
Titer 效价
Pfu 噬斑形成单位