病毒的基因组与结构

1、Viral Genome and Structures http:/ Breakthrough in 1950s The viral nucleic acid genome carries the information needed to replicate, build, and spread virions in the world. One of the building blocks of Molecular Biology T4, TMV Hershey-Chose experiment with phage T4 Fraenkel-Conrats work with TMV Se

2、ven Genome Types Either DNA or RNA Structurally diverse: linear, circular, segmented, gapped, single-stranded (+) strand, single-stranded (-) strand, single stranded (ambisense), double-stranded, some have covalently attached proteins, some have cross-linked ends of double-stranded DNA RNA World hyp

3、othesis What information is encoded in a viral genome？ Replication of viral genome Assembly and packaging of the genome Regulation and timing of the replication cycle Modulation of host defenses Spread to other cells and hosts Information Not contained in viral genomes No genes encoding the complete

4、 protein synthesis machinery No genes encoding protein involved in energy production or membrane biosynthesis No classical centromeres or telomeres found in standard host chromosomes The Baltimore System Viral genome must make mRNA that can be read by host ribosomes NOT all(+) RNA is mRNA Each way h

5、as unique polymerase, primer, template and termination requirements Each virus family has its own characteristic genome strategy Seven classes distinguished by genome replication strategies ds DNA, ss DNA ds RNA, +ss RNA, -ssRNA, Retro dsDNA genomes The problem of replicating the ends of linear DNA

6、molecules through the use of RNA primers. Circular ds DNA genomes that are replicated in the nucleus Linear ds DNA genomes that are replicated in the nucleus Linear ds DNA genomes that are replicated in the nucleus ds DNA genomes that are replicated in the cytoplasm ssDNA genomes A basic problem wit

7、h a ssDNA genome: RNA can only be made from a dsDNA template, ssDNA must be converted into dsDNA before mRNA is made DNA synthesis must precede mRNA production Linear ss DNA genomes that are replicated in the nucleus RNA genomes Cells have NO RNA-dependent RNA polymerases (RdRp) to replicate the gen

8、omes of RNA viruses, or to make mRNA from RNA RNA virus genomes encode novel RdRp Polymerases produce both RNA genomes and mRNA from RNA templates +ssRNA, -ssRNA, dsRNA +ssRNA Hepatitis A virus, foot and mouth disease virus, and rhinoviruses which cause the common cold. The coronaviruses which inclu

9、des important veterinary viruses and the SARS virus. Hepatitis C virus. Yellow fever virus. Positive-strand RNA viruses that make no subgenomic mRNAs Positive-strand RNA viruses that make one or more subgenomic mRNAs -ssRNA RdRp Reassortment: Influenza virus Negative-strand RNA viruse Ambisense RNA

10、viruse Double-stranded RNA(dsRNA) Many dsRNA genomes are segmented dsRNA cannot be translated by ribosomes ds RNA viruses Retrovirus HIV HTLV Integrate into the host DNA HBV Retroviruses Hepadnaviruses Structure Nanometer: 10-9 meters Atom: 0.2-0.3 nm diameter Alpha helix in protein: 1 nm diameter D

11、NA: 2 nm diameter Ribosome: 20 nm diameter Poliovirus: 30 nm Mimivirus: 750 nm Functions of virion proteins Protection of the genome Assembly of a stable, protective protein shell Specific recognition and packaging of the nucleic acid genome Interaction with host cell membranes to form the envelope

12、Delivery of the genome Binding to host cell receptors Transmission of signals that induce uncoating of the genome Induction of fusion with host cell membranes Interaction with cell components to direct transport of genome to the appropriate sit Other interactions with host With cell components to en

13、sure efficient infectious cycle With cell components for transport to sites of assembly With the host immune system Virus particles are not inert structures Virions are metastable structures: have not attainted minimum free energy conformation Gained only when an unfavorable energy barrier is surmou

14、nted, following irreversible conformational changes during attachment and entry Viruses are molecular machines that play active role in delivery of genome To be infectious, the particles must be metastable Must protect the genome (stable) Must come apart quickly on infection (unstable) An infectious

15、 virion is a molecular machine Has moving parts and does work Virion structure and function Structure (the particles; the virion) Created by symmetrical arrangement of many identical proteins to provide maximal contact and non-covalent bonding Function (genome delivery) Made possible because the str

16、ucture is Not permanently bonded together Can be taken apart or loosened on infection to release The tools of viral structural biology Electron microscopy X-ray crystallography Cryo-electron microscopy Nuclear magnetic resonance spectroscopy (NMR) TITLE: Artificial Nano “T4 Bacteriophage”Description

17、: “T4 Bacteriophage” is a virus like the robot in the living body.Artificial nano “T4 Bacteriophage” was fabricated by FIB-CVD on Si surface.Size of the artificial nano “T4 Bacteriophage” is about ten times as large as the real virus.It is made of Diamond-like Carbon. It is likely to begin to walk i

18、n the nano space! Magnification: 25,000XInstrument: SII NanoTechnology Inc. / SMI2050MS2Submitted by: Reo Kometani multiples of 60 are common (60, 180, 240, 960) (T number) Clue 2: Spherical viruses come in many size, but capsid proteins are 20-60 kDa average Triangulation number, T Quasiequivalence

19、 Structurally complex capsids Capsid can be covered by host membranes: enveloped virions Enveloped virions are common, particularly those that infect animals Envelope is lipid bilayer derived from host cell Envelope acquired by budding of nucleocapsid through a cellular membrane Assembly of helical

20、nucleocapsids Assembly of isometric nucleocapsids Acquisition of the lipid envelope Other virion components Enzymes Polymerases, integrases, proteases Activators, mRNA degradation, required for efficient infection, mRNA Cellular components: Histones, tRNAs, myristate, lipid VIPERdb V http:/ ds RNA, +ss RNA, -ssRNA, Retro Positive-strand RNA viruses that make one or more subgenomic mRNAs Double-stranded RNA(dsRNA) Many dsRNA genomes are segmented dsRNA ca