Virus Structure Tutorial

Shuchismita Dutta, Ph.D.

RCSB PDB, 2008

Introduction

• Viruses can cause a variety of diseases from common cold and the flu to serious illnesses such as AIDS, dengue fever, measles, small pox and bird flu.

• All viruses infect cells and hijack the host cellular machinery for their own benefit.

• Learning about the biology and structure of viruses can help us better understand the diseases that they cause, their prevention and treatment.

Goal

• Introduction to viruses – what they are made of, how do they survive and propagate.

• Virus structures – shape and symmetric interaction of proteins, nucleic acids.

• Hands-on activities • List of related resources and additional reading

material. • Take home message: The shape and structure

of proteins are specific for their function.

Overview

• Information– Protein Data Bank – Viruses

• Building virus models– Paper models– Marshmallow models

• Dengue virus – Virus maturation

• Possible directions for lesson plans

Basic Information

1

2

3

What is a virus?

• Organism that causes diseases– Common cold– Flu– AIDS– Bird flu– Polio

Electron micrographs of viruses.

HIV Aeromonas virus 31 Influenza virus

Orf virusHerpes simplex virusSmallopx virus

What do Viruses look like?

Tailed phages

Are viruses living or non-living? (A typical virus life-cycle)

http://www.microbiologybytes.com/introduction/structure.html

http://www.cliffsnotes.com/WileyCDA/CliffsReviewTopic/Viral-Structure-and-Replication.topicArticleId-8524,articleId-8448.html

Viral Infection and Immunity

Poliovirus and RhinovirusAugust 2001 Molecule of the Month

Building Icosahedral Viruses

What is an Icosahedron?

Icosahedron: a geometric solid with twenty faces. Each face is an equilateral triangle and every vertex of the icosahedron is formed by five triangular faces. Edges 30; Vertices 12; Faces 20

The Marshmallow model

Students make marshmallow icosahedrons at Princeton Science & Engineering Expo

The Paper Model

Students make marshmallow icosahedrons at Princeton Science & Engineering Expo

The Story of Dengue Virus

Dengue Virus

• Single-stranded RNA virus

• Causes dengue hemorrhagic fever

• Transmitted by mosquitoes (Aedes aegypti)

• Serotypes (DEN-1, 2, 3, 4)

Dengue Virus

Nature Structural Biology  10, 907 - 912 (2003)

Where?

World distribution of dengue viruses and their mosquito vector, Aedes aegypti, (2005)

Life Cycle of Dengue Virus

Nature Reviews Microbiology 3, 13-22 (January 2005)

Structural changes in envelope protein, icosahedral shell:•Fusion –antiparallel homodimers to parallel homotrimers•Maturation – conformational change of immature trimers to homodimers followed by protease cleavage (by furin) to form mature antiparpllel dimers

Maturation of Dengue Virus

Science 28 March 2008:Vol. 319. no. 5871, pp. 1834 - 1837

Nature Reviews Microbiology 3, 13-22 (January 2005)

Molecule of the Month, July, 2008

Maturation &

Fusion

Possible Directions for Lesson Plans

A Lesson on Icosahedral Viruses

• Shapes of proteins (Introduction to PDB)

• What is a virus?

• Shapes of viruses

• Building 3-D models of icosahedral viruses

• Answering questions about viruses and the icosahedral virus models.

• Research on a specific disease caused by a virus (e.g. Dengue Fever)

VirusesViruses

Protein Structure•Structure of proteins in virus shells•Use of symmetry in assembling viruses

Math & Geometry•Icosahedrons, •helices etc.

Vaccines and Antivirals•Infection, Prevention & Treatment•Rhinovirus or Flu virus or HIV etc.

Genetics & Mutation•Evolution in viruses•Why antiviral treatments need to evolve too

Biotechnological uses of Viruses•Protein expressing,

•gene therapy

Transcription/Translation•How viruses hijack host cells•Viruses and cancer

Acknowledgements

Operated by two members of the RCSB:

Supported by:

NIGMS

The RCSB PDB is a member of the