Viral Structure

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

Structural Components• Viral Capsid

– Capsid means “box”• Capsid can be square, tetrahedron or icosahedron

– Capsid is made up of protein– Capsid is the storage site for genome– Many capsids have a ‘shell’ structure– Genome + Capsid = Nucleocapsid– Capsid is made up of polymeric proteins to conserve genome

• Ex. 5 Kb genome requires 30,000 a/a capsid, which means 90 Kb genome just for capsid!!

• Solution: use multiple copies of same protein• Viral Envelope

– It is the covering of the nucleocapsid– Made up of a phospholipid bilayer– It should allow for attachment of virus on to new host

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

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

•Desmodium Yellow Mottle Virus

•X-Ray Crystallography

•Icosahedral Symmetry

Other Structural Symmetries

Fig. 2.7 The helical nucleocapsid of tobacco mosaic virus.

Other Structural Proteins• Core Proteins

– Can originate from host• Ex. Histones

– Can also be virally coded– Their function is to condense viral genome

• Scaffolding Proteins– Facilitate capsid formation– Facilitate docking of proteins– Facilitate stability of proteins during assembly– Not included inside virion

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

Viral Glycoproteins• Glycoproteins

– 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

Viral Budding

• Several budding mechanims exist• Envelope proteins create 2-D pools excluding cellular

memberane proteins• Capsids can bind ‘cytoplasmic’ tails of envelope

proteins– Binding of capsid proteins and envelope proteins is

mediated by matrix proteins in viruses with helical nucleocapsids (Ex. influenza budding)

• When budding takes place eventually, capsid ‘wraps’ itself around host plasma membrane

Influenza Viral Budding

Matrix protein (M) interacts with HA and NAHA are glycoproteins on envelopeInteraction occurs at the level of their cytoplasmic tail

M protein also interacts with helical nucleocapsid proteins RNP

Semliki Forrest Viral Budding

Direct interaction between icosahedral capsid and envelope proteinsNo Matrix protein involvedInteraction at the level of cytoplasmic tail of envelope protein