Viral Structure

1. Viral Structure

3. 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

4. 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

5. 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

6. 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

8. Desmodium Yellow Mottle Virus • X-Ray Crystallography • Icosahedral Symmetry

9. Other Structural Symmetries Fig. 2.7 The helical nucleocapsid of tobacco mosaic virus.

10. 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

11. 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

12. 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

13. 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

14. Influenza Viral Budding • Matrix protein (M) interacts with HA and NA • HA are glycoproteins on envelope • Interaction occurs at the level of their cytoplasmic tail • M protein also interacts with helical nucleocapsid proteins RNP

15. Semliki Forrest Viral Budding • Direct interaction between icosahedral capsid and envelope proteins • No Matrix protein involved • Interaction at the level of cytoplasmic tail of envelope protein