1. Virus Structure
Chapter 3

2. Tools for Studying Viral Structure
Electron Microscopy
Excellent tool with some limitations
High resolution
Image can be a distortion due to specimen processing
X-ray Diffraction
Good for naked virions (no envelope)
Cryoelectron Microscopy
Flash frozen with liquid nitrogen

3. The “virion” Remember what it is? Also known as a viral particle
Outside the host cell the virus exists as a virion.
Role of the virion:
Protects viral genome
Helps it gain entry to host cell

4. Structure of a Virus Questions Relating to Structure
Is it rigid?
How big is it?
Is it flexible
Structure Must Serve Virus
It should provide protection for genome
It should allow virus to move from one host to next
It should allow for attachment of virus on to new host

5. Viral Genomes

6. Most fungal viruses have dsRNA genomes,
Most plant viruses have ssRNA genomes and
Most prokaryotic viruses have dsDNA genomes

7. Viral Genome Primary structure – encodes proteins required by virus
Secondary and tertiary structures also found as a way the virus controls gene expression.
pseudoknots: enzyme activity, ribosomal frameshifting
Internal ribosome entry sit (IRES)

10. Modifications at the ends of virus genomes
covalently linked protein at the 5 end. In at least some viruses this is a vestige of a primer that was used for initiation of genome synthesis
Some genome RNAs have one or both of the modifications that occur in eukaryotic messenger RNAs (mRNAs): a methylated nucleotide cap at the 5 end and a sequence of adenosine residues (a polyadenylate tail; poly(A) tail) at the 3 end
The genomes of some ssRNA plant viruses are base paired and folded near their 3 ends to form structures similar to transfer RNA. These structures contain sequences that promote the initiation of RNA synthesis

11. Proteins non-covalently associated with virus genomes
Many nucleic acids packaged in virions have proteins bound to them non-covalently.
Rich in the basic amino acids lysine, arginine and histidine, which are –ve able to bind strongly to the +ve charged nucleic acids.
Papillomaviruses and polyomaviruses, (DNA viruses), have cell histones bound to the virus genome.
Most proteins associated with virus genomes, however, are virus coded, e.g HIV-1 nucleocapsid protein that coats the virus RNA; 29 per cent of its amino acid residues are basic.
Nucleic-acid-binding proteins may have other characteristics, such as zinc fingers the HIV-1 nucleocapsid protein has two zinc fingers.
In some viruses, such as tobacco mosaic virus, the protein coating the genome constitutes the capsid of the virion.

12. Segmented genomes
Genes of some viruses encoded in two or more nucleic acid molecules.
Segmented genomes are much more common amongst RNA viruses than DNA viruses
Influenza A Virus

13. Repeat sequences
The genomes of many viruses contain sequences that are repeated.
These sequences include promoters, enhancers, origins of replication and other elements involved in virus replication.
Many linear virus genomes have repeat sequences at the ends (termini), in which case the sequences are known as terminal repeats
If the repeats are in the same orientation they are known as direct terminal repeats (DTRs),
Repeats in the opposite orientation they are known as inverted terminal repeats (ITRs).

15. Virus proteins Small genome viruses
The virion of tobacco mosaic virus contains only one protein species.
The virions of parvoviruses contain two to four protein species. These are viruses with
As the size of the genome increases, so the number of protein species tends to increase
Large genome viruses
The virion of herpes simplex virus 1 contains 39 protein species
The virion of the algal virus Paramecium bursaria Chlorella virus 1 contains over 100 protein species

16. Structural Proteins
Proteins that are components of virions are known as structural proteins.
Functions:
protection of the virus genome
attachment of the virion to a host cell (for many viruses)
fusion of the virion envelope to a cell membrane (for enveloped viruses)

17. Non-structural proteins
Proteins synthesized by the virus in an infected cell but they are not virion components).
Functions:
enzymes, e.g. protease, reverse transcriptase
transcription factors
primers for nucleic acid replication
interference with the immune response of the host.

18. Names of Viral Proteins
Structural proteins VP1, VP2, VP3, (VP = virus protein)
Non-structural proteins: NSP1, NSP2, NSP3,
Many virus proteins are known by an abbreviation of one or two letters, which may indicate:
a structural characteristic G (glycoprotein)
P (phosphoprotein)
or a function F (fusion)
P (polymerase)
RT (reverse transcriptase).

19. Viral Capsid Characteristics:
Protection – without capsid the genome is more susceptible to being inactivated.
Recognize and attach to host cell and then be able to release the genome.
A lipid envelope surrounds capsid in some viruses
An additional protein layer might also surround the capsid which is called the nucleocapsid.

20. Structural Symmetries
Icosahedral Symmetry
20 triangular faces
It is a common capsid structure
Examples of viruses with icosahedral symmetry
Parvoviruses
These are simple viruses
5 Kb ssDNA genome
Capsid is formed with 60 copies of single protein
Protein is approximately 520 a/a
1/3 of genome is dedicated to capsid
Polio virus
Uses 180 copies of 3 subunit proteins
Much bigger virus

21. Viral Envelope Lipid bilayer Most originate from cellular host
Cholesterol and glycoproteins are present
In cases where budding occurs at the plasma membrane (Ex. Influenza) envelope resembles host’s plasma membrane i.e cholesterol and phospholipids
In cases where budding occurs at the ER (Ex. Flaviviruses) envelope has less cholesterol, similar to ER

22. Capsid
Helical
Icoshaderal

23. Icosahedral capsids
a) Crystallographic structure of a simple icosahedral virus.
b) The axes of symmetry

24. Helical Symmetry
The simplest way to arrange multiple, identical protein subunits is to use rotational symmetry & to arrange the irregularly shaped proteins around the circumference of a circle to form a disc.
Multiple discs can then be stacked on top of one another to form a cylinder, with the virus genome coated by the protein shell or contained in the hollow centre of the cylinder.
Tobacco mosaic virus (TMV) is representative of one of the two major structural classes seen in viruses of all types, those with helical symmetry.

25. Enveloped helical virus
Enveloped icosahedral virus

26. Enveloped Structure of HIV
Transmission Electron Micrograph of HIV-1
The nucleocapsid (arrows) can be seen within the envelope.
Enveloped Structure of HIV

28. RNA viruses
From Principles of Virology Flint et al ASM Press

29. DNA viruses
From Principles of Virology Flint et al ASM Press

30. Viral Glycoproteins Glycoproteins Ectodomain
Short cytoplasmic tail
Hydrophobic segment for anchoring (~20 amino acids)
Relatively large ectodomain (external domain)
Ectodomain
Extensively glycosylated preventing aggregation of virions
Glycosylation attracts water and reduces sticking (carried out in ER)
Palmitoylation of cysteine residues is also extensive (carried out in ER)
Most envelope proteins are type I
That means N-terminus facing out, C terminus near anchor domain
Some though are type II