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Introduction to Structural and Molecular Virology

Introduction to Structural and Molecular Virology. Yaroslav Daniel Bodnar University of Illinois at Urbana-Champaign. Viruses Highlight Some Big Ideas. Structure- Dynamics -Function relationships. A systems perspective: Understanding of complex function by looking at its components.

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Introduction to Structural and Molecular Virology

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  1. Introduction to Structural and Molecular Virology Yaroslav Daniel Bodnar University of Illinois at Urbana-Champaign

  2. 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.

  3. Size Matters: Definition of a Virus

  4. A Few Surprises • Mutual symbiosis between Polydnaviruses and parasitic wasps. • Oncolytic Virotherapy: Seneca Valley Viruses

  5. Wendell M. Stanley1946 Nobel Prize in ChemistryCrystallized Tobacco Mosaic Virus andSystematically Investigated its Biochemistry

  6. Structural Biology

  7. A Trip Inside of HPV PLAY MOVIE 1 (HPV Density Map)

  8. A Trip Inside of HPV

  9. 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.

  10. Symmetry of Viral Capsids Icosahedral Helical

  11. Enveloped Viruses

  12. Survey of Human Viruses

  13. Principles of Viral Capsid Architecture

  14. AsymmetricSubunit • 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.

  15. The Jelly-Roll Fold

  16. Repeat the Asymmetric Subunit to “Tile” the Surface of the Capsid

  17. “Quasi-Equivalence” is a Necessary Property of Enclosed Surfaces

  18. 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!

  19. Play Movie 2 (Harrison; Virus Capsid Dynamics)

  20. Formation of New Viruses by Self-Assembly

  21. You can make viruses in a test tube! Play Movie 3 (Virus Self-Assembly)

  22. The Viral Life Cycle

  23. Host Cell Entry By Membrane Fusion

  24. Play movie at: http://www.molecularmovies.com/movies/gp41_061008.html

  25. The Viral Life Cycle

  26. 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

  27. 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?

  28. 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.

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