Guest lecture

ONE WAY WE STUDY VIRUSES IN THE TESCHKE LAB

Introduction

  • Overview of the Teschke Lab's focus on studying viruses.

Geographic Scope

  • Map Depiction of Geographic Reach: Showcases various US states and other regions involved in virus research or education, likely to illustrate collaboration or influence across a wide area including: Washington, North Dakota, Massachusetts, and Hawaii.

  • Differentiates between local institutions like UW-Eau Claire and national entities such as MIT.

Understanding Viruses

Defining Viruses

  • What is a Virus?: Viruses are smaller than their host cells and come in diverse structures.

  • Bacterial Viruses: Commonly known as bacteriophages or phages.

  • Core Characteristics:

    • Obligate Parasite: Viruses cannot reproduce independently and must hijack a host cell for replication.

    • Viral Genome: Composed of either DNA or RNA, usually in a sparse configuration.

    • mRNA Production: All viruses generate mRNA that relies on host ribosomes for translation into proteins.

    • Receptor-Binding Proteins: Necessary for the virus to attach and enter host cells.

    • Infectious Genome: The viral genome can be infectious and can also incorporate into cellular chromosomes, particularly seen in retroviruses and some phages.

  • Reference adaptation from Flint, S.J., et al. (2003).

Structure and Function of Viruses

Virus Sizes and Magnifications

  • Size Comparison: Most viruses range from less than 30 nanometers to over 500 nanometers in diameter, vastly smaller than typical eukaryotic cells.

  • Visual Reference: Illustrations are displayed at 900,000x magnification.

Examples of Specific Viruses
Dengue Fever Virus

  • Commonly causes flu-like symptoms, potentially lethal in severe cases.

  • Reference PDB ID: 1k4r.

Rhinovirus

  • One of the viral agents responsible for the common cold.

  • Reference PDB ID: 1rhv.

Tobacco Mosaic Virus

  • The first virus to be discovered, exhibiting stability in external environments.

  • Reference PDB ID: 3j06.

Foot and Mouth Disease Virus

  • Causes significant health issues in livestock, characterized by fever and blisters.

  • Reference PDB ID: 1bbt.

Feline Distemper Virus

  • A severe infection in cats, preventable by vaccination.

  • Reference PDB ID: 1c8e.

Virus Shapes

  • Polyhedral (Icosahedral) Viruses: Features symmetrical protein shells.

  • Helical Viruses: Structure involves nucleic acid wound inside a cylindrical protein capsid.

  • Complex Viruses: Composed of various proteins forming intricate structures for protection and infection mechanisms.

  • Enveloped Viruses: Surrounded by a membrane studded with glycoproteins facilitating cell infection (e.g., influenza, HIV).

Structural Assembly

  • Viruses encounter a constraint where their genomes must encode all required proteins while fitting into a small capsid. Solutions include:

    • Modular Approach: Utilizes multiple identical protein subunits to create large capsids.

    • Symmetrical Structures: Small viruses may use 60 identical proteins for a compact genome allowing for basic functions. Larger viruses can employ various proteins in quasi-symmetrical arrangements to encase more complex genomes.

  • Overall Proteins Count: Range from 60 to 960 proteins depending on the virus.

Morphological Diversity of Phages

Classifications of Phages

  • Families of Phages: Includes groups like Myoviridae, Siphoviridae, and Cystoviridae.

  • Distinctive Features: Each family exhibits unique morphological traits, including tail structures and capsid forms.

Visualization of Viruses

Microscopy Techniques

  • Many viruses require electron microscopy for visualization due to their minute size.

  • Importance of tools like cryogenic electron microscopy (cryoEM) for detailed structural analysis.

Importance of Studying Viruses

Ecological and Biological Context

  • Viruses in Life: Humans and ecosystems encounter billions of viruses daily, influencing health and biological functions.

  • Learning through virus-infected cells provides insight into host organism biology.

Bacteriophages as a Study Model

  • Target bacterial infections effectively, presenting opportunities for therapies and biotechnological applications. Referenced article in Nature Reviews Microbiology (2018).

Overall Phage Abundance

  • Global Statistics: Over 103110^{31} bacteriophages exist in Earth's waters:

    • Each phage weighs approximately 10−1510^{-15} grams.

    • Bacteriophage biomass exceeds elephants' biomass by a factor of 10,000.

    • The cumulative length of 103110^{31} phages would span over 200 million light-years.

Study Theories and Topics

Case of Phage P22 Morphogenesis

  • Assembly Process: Involves complex steps: absorption, tail tube assembly, DNA ejection, and lysis for phage release.

    • Explore how scaffolding protein influences portal ring formation and assembly fidelity.

Structural Investigations

  • CryoEM: Employed to assess the interaction between scaffolding proteins and portal proteins within procapsids.

  • Inquiry into structural differences post-mutations in coat protein affecting morphogenesis fidelity.

Innovations in Viral Research

  • New technologies expedite understanding protein structure and function.

  • Structure-based drug design using AI for efficient identification of drug interactions, enhancing drug discovery cycles.

Conclusions

  • Scaffolding proteins play a pivotal role in the assembly and functionality of phages.

  • The integration of AI-enabled techniques with cryoEM promises advancements in virology and therapeutic development.

Acknowledgments

  • Recognition of contributions and advancements in the field of virology and the study of viral structures is noted.

Questions and Further Discussion

  • Open the floor to questions, promoting active engagement with the content covered.