病毒的基因组与结构

• NOT all(+) RNA is mRNA
• Each way has unique polymerase, primer, template and termination requirements
• Each virus family has its own characteristic genome strategy
Double-stranded RNA(dsRNA)
• Many dsRNA genomes are segmented • dsRNA cannot be translated by ribosomes
ds RNA viruses
• HIV • HTLV
Retrovirus
• Integrate into the host DNA • HBV
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 molecules through the use of RNA primers.
Viral Genome and Structures
Laboratory of Medical Molecular Virology Chang Liu
http://v.163.com/special/opencourse/virology.html
Breakthrough in 1950’s
The tools of viral structural biology
• Electron microscopy • X-ray crystallography • Cryo-electron microscopy • Nuclear magnetic resonance spectroscopy
segmented, gapped, single-stranded (+) strand, single-stranded (-) strand, single stranded (ambisense), double-stranded, some have covalently attached proteins, some have crosslinked ends of double-stranded DNA • RNA World hypothesis
Positive-strand RNA viruses that make one or more subgenomic mRNAs
-ssRNA
• RdRp • Reassortment: Influenza virus
Negative-strand RNA viruse
Ambisense RNA viruse
Functions of virion proteins
• Protection of the genome
– Assembly of a stable, protective protein shell – Specific recognition and packaging of the nucleic
• Function (genome delivery)
– Made possible because the structure is Not permanently bonded together
– Can be taken apart or loosened on infection to release
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
• An infectious 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
Information Not contained in viral genomes
• No genes encoding the complete protein synthesis machinery
• No genes encoding protein involved in energy production or membrane biosynthesis
– 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 genomes of RNA viruses, or to make mRNA from RNA
• 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
• 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
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
Retroviruses
Hepadnaviruses
Structure
• Nanometer: 10^-9 meters • Atom: 0.2-0.3 nm diameter • Alpha helix in protein: 1 nm diameter • DNA: 2 nm diameter • Ribosome: 20 nm diameter • Poliovirus: 30 nm • Mimivirus: 750 nm
– With cell components to ensure efficient infectious cycle
– With cell components for transport to sites of assembly
– With the host immune system
Virus particles are not inert structures
acid genome – Interaction with host cell membranes to form the
envelope
• Delivery of the genome
– Binding to host cell receptors – Transmission of signals that induce uncoating of
• The coronaviruses which includes important veterinary viruses and the SARS virus.
• Hepatitis C virus. • Yellow fever virus.
Positive-strand RNA viruses that make no subgenomic mRNAs
(NMR)
TITLE: Artificial Nano “T4 Bacteriophage” Description: “T4 Bacteriophage” is a virus like th
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ds DNA genomes that are replicated in the cytoplasm
ssDNA genomes
A basic problem with a ssDNA genome: •RNA can only be made from a dsDNA template,
– ssDNA must be converted into dsDNA before mRNA is made
• T4, TMV
Hershey-Chose experiment with phage T4
Fraenkel-Conrat’s work with TMV
Seven Genome Types
• Either DNA or RNA • Structurally diverse: linear, circular,
• 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)
• Virions are metastable structures: have not attainted minimum free energy conformation
• Gained only when an unfavorable energy barrier is surmounted, following irreversible conformational changes during attachment and entry
• 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.
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