20. Structure of Viruses
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Virology
The study of viruses.
Virus
An obligate intracellular parasite containing a nucleic acid genome surrounded by a protein capsid and sometimes an envelope.
Why are viruses obligate intracellular parasites?
They require a host cell to replicate.
Virion
A complete infectious virus particle outside a host cell.
What are the basic components of a virion?
Genome, capsid, and sometimes an envelope and viral enzymes (replicative enzymes).
Can viruses contain both DNA and RNA genomes?
No, viral genomes are either DNA or RNA.
Single stranded or Double stranded
How are viruses metastable structures?
Viruses are metastable structures because their protein capsids exist in a high-energy, "spring-loaded" state that is stable enough to protect the viral genome outside a host, yet primed to come apart when the right cellular trigger is applied
Difference between a virus particle and a virion?
Virion: complete, inert, infectious viral particle that exists outside of a host cell. Its main job is to transport viral genetic material (DNA or RNA) wrapped in a protein coat (capsid) from one host cell to another.
Virus: "Virus" is a broader, more general term. It can refer to the taxonomic group, the entire lifecycle of the agent, or the viral machinery and genetic material operating inside a host cell during replication
Viral genome
The genetic material of a virus.
What forms can viral genomes take?
DNA or RNA, single-stranded or double-stranded, linear, circular or segmented.
Capsid
The protein shell surrounding a viral genome.
helical, icosahedral or complex structure
Functions of the capsid
Protection of nucleic acid (extracellularly or intracellularly)
specificity for attachment (non-enveloped viruses)
transport nucleic acid from cell to cell
transport nucleic acid to the site of replication: nucleus, cytoplasm, ER etc
packaging
Why does the capsid aid in packaging?
Nucleic acids are negatively charged, so will repel when folded, so some capsid proteins will neutralise the charge for folding
Why is the capsid important?
It protects the genome and enables infection of new host cells.
Nucleocapsid
The viral genome together with its capsid.
Envelope
A host-derived lipid membrane surrounding some viruses.
What is the complete structure of an enveloped virus?
Genome + capsid + envelope.
What is the complete structure of a non-enveloped virus?
Genome + capsid.
Structural unit
The smallest functional building block of a capsid.
Capsomer
A morphological unit visible on the surface of some virus particles.
Why can't viral genomes encode huge capsid proteins?
Viral genomes are generally too small to encode a single large protective protein shell.
What did Watson and Crick propose in 1956?
Viral capsids are built from many identical protein subunits arranged symmetrically.
Why are viral capsids built from repeating subunits?
Genetic economy, symmetry and structural stability.
Genetic economy
Building a large structure using many copies of a small number of proteins.
Why is symmetry advantageous in viral capsids?
It allows identical interactions between subunits and stabilises the structure.
Major types of capsid symmetry
Helical, icosahedral and complex.
Helical capsid
A capsid in which protein subunits are arranged in a spiral around the genome.
What does a helical virus resemble?
A hollow tube with the genome running through the centre.
What determines the length of a helical virus?
The size of the genome.
Example of a helical virus
Tobacco mosaic virus (TMV).
Why are many RNA viruses helical?
The helical arrangement complements the structure of nucleic acids.
Pitch
The distance moved along the axis in one complete turn of a helix.
Axial rise per subunit
The distance each subunit contributes along the helical axis.
Icosahedral capsid
A capsid with 20 triangular faces and high rotational symmetry.
How many faces does an icosahedron have?
20.
How many vertices does an icosahedron have?
12.
Why are icosahedral capsids common?
They provide maximum volume with minimal protein.
Example of an icosahedral virus
Poliovirus.
How many capsid proteins does poliovirus contain?
Four capsid proteins present in 60 copies each.
Complex virus
A virus that cannot be classified as purely helical or purely icosahedral.
Examples of complex viruses
Bacteriophages, poxviruses and herpesviruses.
Why are bacteriophages considered structurally complex?
They contain distinct head, tail and attachment structures.
Why are poxviruses considered structurally complex?
They possess elaborate virion architecture not based on simple helical or icosahedral symmetry.
What is a bacteriophage?
A virus that infects bacteria.
Why have bacteriophages been important in biology?
They were key models for understanding viral replication and molecular genetics.
What important molecular biology tools originated from phages?
T4 DNA ligase, T7 DNA polymerase, lambda vectors and T7 promoters.
What is a herpesvirus tegument?
A protein layer between the capsid and envelope.
Why are herpesviruses structurally complex?
They contain a capsid, tegument, envelope and many proteins.
Approximately how many proteins may be present in a herpesvirus particle?
More than 80.
Electron microscopy (EM)
A method for visualising virus particles using electrons.
What is the typical resolution of conventional EM mentioned in the lecture?
Approximately 50–70 Å.
Why is EM useful?
It reveals particle morphology and overall structure.
Cryoelectron microscopy (Cryo-EM)
A structural method in which samples are rapidly frozen and imaged in a near-native state.
Why is cryo-EM advantageous?
It preserves native structure and allows high-resolution 3D reconstruction.
Modern cryo-EM resolution
Approximately 2–3 Å.
Why has cryo-EM become so important in virology?
It can reveal near-atomic structural details without crystallisation.
X-ray crystallography
A technique used to determine atomic structures from protein crystals.
What is X-ray crystallography commonly used for in virology?
Determining detailed protein and capsid structures.
Difference imaging
A method that combines cryo-EM maps with X-ray structures.
Why is difference imaging useful?
It helps identify the location of proteins within complex virus particles.
Virus envelope composition
A host-derived lipid bilayer containing viral glycoproteins.
Where does the viral envelope come from?
Host cell membranes.
Can viral envelopes contain host molecules?
Yes.
Viral glycoprotein
A viral membrane protein embedded in the envelope.
Major regions of a viral glycoprotein
Ectodomain, transmembrane region and cytoplasmic domain.
Ectodomain
The external region of a viral glycoprotein.
Functions of the ectodomain
Receptor binding, antibody recognition and membrane fusion.
Transmembrane domain
The region anchoring the glycoprotein in the membrane.
Cytoplasmic domain
The internal region interacting with viral structural proteins.
Why are viral glycoproteins important?
They mediate entry into host cells.
How do enveloped viruses acquire their envelope?
By budding through a host membrane.
Budding
A release process in which a virus acquires a host-derived membrane envelope.
Can different viruses bud from different host membranes?
Yes, plasma membrane, ER or Golgi membranes may be used.
Virus assembly
The process by which new virions are formed.
Major stages of virus assembly
Structural protein synthesis, assembly, genome packaging, envelope acquisition, release and maturation.
Why are viruses assembled from subunits?
It is more efficient and energetically favourable than assembling a complete particle at once.
Genome packaging
The incorporation of the viral genome into a newly forming particle.
Virion maturation
Structural changes that convert immature particles into infectious virions.
Metastable structure
A structure that is stable but capable of rapid rearrangement when triggered.
Why are virus particles described as metastable?
They must remain stable outside cells yet disassemble during infection.
What triggers viral disassembly?
Receptor binding, pH changes or intracellular conditions.
Why must virions be stable outside cells?
To protect the genome during transmission.
Why must virions disassemble inside cells?
To release the viral genome for replication.
Why is metastability important?
It balances protection and infectivity.
Segmented genome
A viral genome divided into multiple nucleic acid segments.
Advantage of genome segmentation
It allows packaging of large genetic information in separate pieces.
Disadvantage of segmentation
All genome segments must be successfully packaged and transmitted.
Multipartite genome
A viral genome divided between different particles.
Disadvantage of multipartite genomes
Multiple particles must infect the same host cell.
Can viral genomes be single-stranded?
Yes.
Can viral genomes be double-stranded?
Yes.
Can viral genomes be circular?
Yes.
Can viral genomes be linear?
Yes.
Why do viruses exhibit such diverse genome structures?
Different genome organisations support different replication strategies.
Why are viruses considered structurally diverse?
They vary in genome type, capsid architecture, envelope presence and complexity.
What are the major learning outcomes of this lecture?
Virion structure, capsid architecture, virus envelopes, structural analysis techniques, virus assembly, metastability and genome diversity.
Why is genetic economy important for viruses?
Small genomes restrict the number of proteins that can be encoded.
Why are repeated protein subunits a clever viral strategy?
A large capsid can be built while encoding only a few proteins.
Why are helical capsids well suited to RNA genomes?
Nucleic acids naturally adopt helical conformations.
Why are icosahedral capsids common in viruses?
They maximise internal volume while minimising protein requirement.