Introduction to Structural and Molecular Virology

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Introduction to Structural and Molecular Virology
Yaroslav Daniel Bodnar University of Illinois at
Urbana-Champaign
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Viruses Highlight Some Big Ideas

• Structure-Dynamics-Function relationships.
• A systems perspective Understanding of complex
  function by looking at its components.
• Self-assembly gives rise to complex forms in
  biological systems.
• Using a simplified model system to understand a
  broad range of more complex phenomena.

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Size Matters Definition of a Virus
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A Few Surprises

• Mutual symbiosis between Polydnaviruses and
  parasitic wasps.
• Oncolytic Virotherapy Seneca Valley Viruses

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Wendell M. Stanley1946 Nobel Prize in
ChemistryCrystallized Tobacco Mosaic Virus
andSystematically Investigated its Biochemistry
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Structural Biology
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A Trip Inside of HPV
PLAY MOVIE 1 (HPV Density Map)
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A Trip Inside of HPV
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What the nucleocapsid and other accessory viral
proteins need to do?

• Protect viral genome needs to be fully enclosed.
• Needs to be inert outside the cell and move
  freely in-search of a new host.
• Needs to be a dynamic structure
• Change (activate) in response to a specific
  stimulus.
• Occurs in a series of programmed stages.

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Icosahedral
Symmetry of Viral Capsids
Helical
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Enveloped Viruses
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Survey of Human Viruses
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Principles of Viral Capsid Architecture
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Asymmetric Subunit

• Each subunit consists of four proteins.
• Capsid proteins interact by highly specific,
  flexible non-covalent contacts.
• Long terminal extensions and loops make each
  viral capsid unique.

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The Jelly-Roll Fold
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Repeat the Asymmetric Subunit to Tile the
Surface of the Capsid
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Quasi-Equivalence is a Necessary Property of
Enclosed Surfaces
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Triangulation Numbers

• How many equilateral triangles can fit on one
  face?
• The size of each capsid protein must stay
  approximately the same.
• How do you make a larger capsid? ...Increase the
  triangulation number!

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Play Movie 2 (Harrison Virus Capsid Dynamics)
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Formation of New Viruses by Self-Assembly
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You can make viruses in a test tube!
Play Movie 3 (Virus Self-Assembly)
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The Viral Life Cycle
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Host Cell Entry By Membrane Fusion
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Play movie at http//www.molecularmovies.com/movi
es/gp41_061008.html
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The Viral Life Cycle
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VIPERdb Exercise 1(http//viperdb.scripps.edu/)

• Explore VIPERdb. Be sure to visit viruses of
  different families and T-numbers. While you surf,
  write down the T-number, excess surface charge,
  and average radius of each virus. Some search
  suggestions include
• Picornaviruses
• POLIO Poliovirus (Type 1 Mahoney strain)?
• POLIO Poliovirus/Receptor Complex
• COMMON COLD Human Rhinovirus 16
• COMMON COLD Human rhinovirus 16 with Receptor
• Hepadnaviruses
• HEPATITIS Human Hepatitis B Viral Capsid
• Papillomaviruses
• HPV (CERVICAL CANCER) Human Papilloma Virus 16
  L1 Capsid

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• Did you find a relationship between the T-number
  and the size of the viruses? Why may this be?
• Clue Most virus capsid proteins are
  approximately the same size.
• Did you notice a trend in the charge of virus
  capsids? Do they tend to be positively or
  negatively charged? Why does this make sense?
• Clue Remember that virus capsids are essentially
  molecular containers. What do they contain?
  What is the charge of the contents?

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VIPERdb Exercise 2

• Load 6 to 10 viruses from the same family into
  STRAP and perform a multi-sequence alignment.
• Choose one of the viruses from above and list
  several of the most highly conserved regions.
• Why do you think that these conserved regions are
  important? What do you think they do? Use
  structural information and other information
  available on VIPERdb to support your answer.
• Suppose you want to identify regions of your
  virus that interact with antibodies. How can you
  use VIPERdb to do this?
• Hint Different strains (or serotypes) of a virus
  are characterized by which antibodies bind to
  them. This means that different strains of the
  same virus will differ in the regions you're
  interested in.