Virus Structures - Lecture 1

Jun 28, 2024

Virus Structures - Lecture 1

Instructor

  • Steven Harrison, Harvard Medical School, Children's Hospital Boston, Howard Hughes Medical Institute

Overview

  • Lecture 1: General features of molecular organization of virus particles.
  • Lecture 2 & 3: Specific properties of virus particles relevant to molecular mechanism of infection in a cell.

Introduction to Viruses

  • Viruses: Carriers of genetic information, acting as extracellular organelles.
  • Virus Particle (Virion): Molecular machine that packages viral genomes, escapes infected cells, transfers to new cells, and initiates replication.

Virus Pathogenicity

  • Pathogens: Viruses hijack cellular biosynthetic machinery for replication.
  • Host Defense Mechanisms: Hosts evolve defenses like the immune system.

Virus Categories

Enveloped Viruses

  • Surrounded by a lipid bilayer membrane from the host cell.

Non-enveloped Viruses

  • Only a protective protein coat, no lipid bilayer.

Structural Examples

Non-enveloped Virus Example: Rotavirus

Enveloped Virus Example: Sindbis Virus

Sizes and Distances

  • Virus particles: ~700 angstroms or 70 nanometers in diameter.
  • Chemical bonds: ~1-2 angstroms in length.
  • Molecular mass: Tens of millions of Daltons.

Key Issues Covered

  1. Symmetry in Non-enveloped and Small Enveloped Viruses
  2. Building Blocks of Virus Particles
  3. Outer Proteins of Enveloped Viruses

Symmetry in Virus Particles

Definition

  • Symmetry: Operation (e.g., rotation) that aligns an object with itself.
  • Icosahedral Symmetry: 5-fold, 3-fold, and 2-fold axes of symmetry.
  • Helical Symmetry: Found in elongated particles like Tobacco Mosaic Virus (TMV).

Icosahedral Symmetry

  • Platonic solid with 20 triangular faces.
  • Example: Parvovirus - Small virus with 60 subunits decorating a shell.

Structural Building Blocks

Jelly Roll Beta Barrel

  • Basic fold visible in many virus coat proteins.
  • Example: Canine Parvovirus - Compact domain elaborated with loops.
  • Positive Strand RNA Viruses: e.g., Polio Virus, Human Rhinovirus.

Larger Genome Packaging

  • Example: Papillomavirus - Uses pentameric building blocks for a double-stranded DNA genome.
  • Importance in human health (e.g., cervical cancer vaccines).

Adenovirus Structure

Hexon Protein

  • Trimeric, two beta jelly roll domains per subunit.

Relevance to Bacteriophages

  • Example: PRD1 - Similar to animal viruses such as adenoviruses.

Packaging Mechanisms

  • Use of inner scaffold proteins for structure and size determination.

Examples

  1. P22 Bacteriophage: Scaffold is reused post-DNA insertion.
  2. Herpes Virus: More complex than bacteriophages with elaborate surface loops.

Enveloped Viruses

Membrane Acquisition

  • Bud out of cell surfaces or internal compartments like ER or Golgi.
  • Smaller envelope viruses: Regular icosahedral symmetry.
  • Larger envelope viruses: Irregular structures e.g., influenza, HIV.

Entry Mechanism

  • Fusion of viral and host cell membranes.
  • Example: Dengue Virus - Conformational change triggered by low pH.
  • Example: Influenza Virus - Hemagglutinin protein (HA) undergoes conformational changes for membrane fusion.

Summary

  • Virus structures involve symmetric and asymmetric arrangements of protein subunits with roles in protection, attachment, and entry into host cells.
  • Future lectures will elaborate on virus entry mechanisms and membrane fusion.