Introduction to Structural and Molecular VirologyYaroslav Daniel BodnarUniversity of Illinois at Urbana-Champaign

Viruses Highlight Some Big IdeasStructure-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.

Size Matters: Definition of a Virus

A Few SurprisesMutual symbiosis between Polydnaviruses and parasitic wasps.Oncolytic Virotherapy: Seneca Valley Viruses

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

Structural Biology

A Trip Inside of HPVPLAY MOVIE 1 (HPV Density Map)

A Trip Inside of HPV

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.

IcosahedralHelicalSymmetry of Viral Capsids

Enveloped Viruses

Survey of Human Viruses

Principles of Viral Capsid Architecture

Asymmetric SubunitEach 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.

The Jelly-Roll Fold

Repeat the Asymmetric Subunit to Tile the Surface of the Capsid

Quasi-Equivalence is a Necessary Property of Enclosed Surfaces

Triangulation NumbersHow 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!

Play Movie 2 (Harrison; Virus Capsid Dynamics)

Formation of New Viruses by Self-Assembly

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

The Viral Life Cycle

Host Cell Entry By Membrane Fusion

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

The Viral Life Cycle

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 ComplexCOMMON COLD: Human Rhinovirus 16COMMON COLD: Human rhinovirus 16 with ReceptorHepadnaviruses:HEPATITIS: Human Hepatitis B Viral CapsidPapillomaviruses:HPV (CERVICAL CANCER): Human Papilloma Virus 16 L1 Capsid

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?

VIPERdb Exercise 2Load 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.