(V) 23: Viral Structure Flashcards
Capsid
viral container or shell
Virion
a complete infectious particle
Nucleocapsid
situation where the capsid also contains the genome
- closely intertwined w/ viral genome
Envelope
lipid bilayer membranes enclosing nucleocapsids
- HOST-DERIVED
acquired by budding nucleocapsid
MOST (not all) viruses have an envelope
Stability of virions
The virion must be BOTH stable and unstable
Unstable IN the cell
Stable when OUTSIDE the cell
When is the virion stable in the infectious cycle? Unstable?
Stable when OUTSIDE the cell
Unstable when INSIDE the cell
Protein functions
Protection of the genome
- assembly of protective shell
- recognition and packaging of nucleic acid genome
- forms envelope
Delivery of the genome
- binding external receptors of host cell
- uncoating of genome
- fusion w/ host cell memb (envelopes)
- transport of genome
Other interactions
- w/ host immune system
- to ensure efficient infectious cycle
Viral Structural Biology Techniques
- electron microscopy
- cryo-electron microscopy
- X-ray crystallography
- nuclear magnetic resonance spectroscopy (NMR)
Electron Microscopy
- negative staining allows to see the shape of virus and envelope
Downside: potential to DESTROY ultrastructural features/structure
Negative staining
stain sample w/ ELECTRON-DENSE materials (to absorb electrons)
- allows to see the virus
Cryo-electron microscopy
- NO stain = structure preservation
- FLASH FREEZE samples and image at very cold temps (freezing is contrast)
- aims to preserve structure
- uses computers to reconstruct images
X-ray crystallography
Key: ability of viral protein/virion to crystallize
- bombard virion w/ X-ray
Ex. “CANYONS” in structure = indentations on cell surface (cell surface receptors to latch onto host receptors)
NMR
Nuclear Magnetic Resonance Spectroscopy
- if your protein does not crystallize
- radiation emitted from nucleus in a magnetic field is measured by spectra
- certain nuclei can have a magnetic moment
Resolution of Viral Structural Biology Techniques
(Most detailed) X-Ray + NMR > Cry-Electron EM > Electron Microscopy
Cry-Electron, EM and X-ray give FULL virion structures whole NMR only gives viral proteins
EM destroys structure w/ stain
What type of viral structural techniques look at the full virion?
Cry-Electron, EM and X-ray give FULL virion structures whole NMR only gives viral proteins
Principles of viral genetic economy
Virions are made from MANY copies of a FEW proteins
- viral genome’s coding capacity is limited
Key is SYMMETRY
- if protein subunits on the surface are identical, then contacts will generate a symmetrical object
Types of symmetry
Helical symmetry
- for ROD-shaped viruses
- ex. tobacco mosaic virus (TMV)
Polyhedral symmetry
- for ROUND viruses
- ex. simian virus 40
Rules of viral symmetry
- Each subunits had identical bonding contacts w/ neighbouring subunits
- one set of protein A + B will interact in a similar way to another protein A + B - Bonds btwn subunits are mostly via NON-COVALENT interactions
- so they can be opened up to expose the genome
HPV Vaccine
Gardasil is the outer shell of HPV
- NOT the genome
Notions on helical symmetry
- a protein subunit interacts w/ an identical protein subunit in an identical manner
- also interacts w/ viral genome
- there are nucleocapsids
- can be composed of one or more types of protein
- nucleoprotein associates w/ viral genome (goal = protect genome)
Ex. measles virus, vesicular stomatitis virus, ebola virus
Nucleoprotein
a part of nucleocapsid
Ebola virus nucleocapsid
VP30, VP24, VP35 are Ebola viral proteins forming the nucleocapsid
Polyhedral capsids
round capsids have a DEFINED number of proteins in multiples of 60
- number of subunits MUST be a multiple of 60
They have ICOSAHEDRAL symmetry
Icosahedron
solid w/ 20 faces
- each face is an EQUILATERAL triangle
allows formation of a closed shell w/ 60 identical subunits (3 x20 = 20 identical trimers)
Axes of symmetry of icosahedral symmetry
Vertice: 5 fold
Face: 3 fold
Edge: 2 fold
Norwalk virus
larger virus
- quasi-equivalent (almost perfect)
Quasiequivalent
ALMOST perfectly symmetrical w/ BIGGER viruses
- LOSE 5 fold symmetry = can lose multiple of 60
- can have more than 5 on some vertices
Poliovirus Capsid Assembly
- P1 precursor peptide is cleaved to generate the protamer (5S)
- 5 protamers = pentamer
Capsids are formed by assembly of 12 pentamers
5S unit can be snipped to make a more compact icosahedral triangle OR P1 peptide can generate 5S
How are envelopes derived from host membranes?
Envelope is acquired by budding nucleocapsid
- viral envelope lipoproteins get placed on cell membrane when ENTERING
- picks up host membrane and viral envelope lipoprotein when they LEAVE
also contain viral envelope glycoproteins
Viral envelope glycoproteins
Envelope viral proteins
key elements that interact w/ host cell receptors