Chapter 6: Viruses and Other Acellular Diseases

Viruses Do More than Cause Disease

Typically thought to be major cause of disease, but are other important uses:

• Vital members of aquatic ecosystems

• Can be used to destroy cancer cells

• Bacteriophages in Human Guts may regulate bacterial microbiome

• Important model organisms

6.1 Viruses Are Acellular

Virology - the study of viruses

 Viruses- infectious agents unique in their simple, acellular organization and pattern of multiplication

Major Causes of Disease

Important model systems in molec bio

 Major Pandemics in History

• See list

Extracellular or Intracellular Viruses

• Extracellualr

  • Inactive

  • Can't reproduce outside of living cells

• Intracellular

  • Takes over host cells

  • Uses them to synthesisize viral compoentns --> mature progeny viruses assembled and released

Viruses Can Infect All Cell Types

Bacteriophages (phages) - infect bacteria

Few archaeal viruses have been identified

Most are eukaryotic viruses

6.2 The Structure of Viruses

Virion- mature virus particle

Virions range in size

• 20nm in diameter

• Size of rod-shaped bacterial cell

• Most viruses must be viewed w an electron microscope

Contents

• Nucleocapsid - composed of nucleic acid (DNA or RNA) + a protein coat (capsid)

• Enveloped viruses 0 lipid membrane

• Nonenveloped viruses (naked viruses)

Basic Viral Structures

Naked vs Enveloped

Capsid

• Protein coat of virus

  • Made of protein subunits called protomers forming capsomer

• Protect viral genetic material

• Help in genetic transfer between host cells

• Shapes:

  • Helical

  • Polyhedral

  • Complex

Viral Capsids

• Rods or Filaments

  • Ebola

  • Tboacco Mosaic Virus

• Geometric Shapes

  • Adenovirus

  • Bacteriophage T4

• Spherical

  • HIV

  • Influenze

  • SARA

  • Smallpox

Helical Capsid

• Shaped like hollow tubes w protein walls

• Protomers self-assmeble into rigid tube

• Size of capsid is influenced by promoters and genome

Polyhedra/Icosahedral Capsids

Icosahedron is a regular polyhedron w 20 triangular faces

Complex Capsids

Some viruses do not fit into the category of having helical or icosahedral capsids

• Poxvirus - larges of the animal viruses

  • Complex interior + ovoid- to brick-shaped exterior

Viral Envelopes + Enzymes

• Many viruses are bound by an outer, flexible, membranous layer called an envelope

• Animal virus envelopes (lipids + carbohydrates) usually arise form host cell plasma  or organelle membranes

Viral Envelop Proteins

Envelope proteins are viral encoded, may form spikes

• Spikes invovled in viral attachment to host cell

• Surface proteins can have enzymatic activity needed for entry or exit from host cell

• Used for ID of virus

Viral Genomes are Structurall Diverse

A virus may have single or double-stranded DNA or RNA

The size of viral genome varies

• 4k nucleotides - 2mil nucleotides

Genomes can be linear or circular

Some RNA viruses have "segmented genomes"

• Provide genetic reassortment among different strains

6.3 Viral Life Cycles Have 5 Steps

One-Step Growth Curve of Virus

Measure the total number of phage progeny (burst size) produced during a single round of infection.

• Burst size

  • 10-100 (DNA virus)

  • Up to 20k (RNA virus)

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Bacterial Growth Curve

Steps

1. Lag Phase

2. Log Phase

3. Stationary Phase

4. Death Phase

[insert graph drawing]

Viral Life Cycles

• Mechanism used depends on viral structure + genome

Five Steps:

1. Attachment (adsoprtion)

2. Entry into the host

3. Synthesis

4. Assembly

5. Viral Particle Release

Step 1. Attachment (Adsorption)

Viruses require a host cell to multiply

Ligand (on virion) attaches to a receptor (on host)

• SARS-CoV-2 spike protein is the viral ligand that attaches to the human recpetor called ACE2

Receptor determines host preference:

• Tropism - viral affinity to specific tissues

In plants, no receptors have been found, instead damage of the host cell is required for entry.

Step 2. Entry Into the Host

• After attachment, the virus's genome or entire nucleocapsid enters the cytoplasm

• Three Methods used

  1. Fusion o fthe virla envelope w host cell's PM

  2. Endocytosis

  3. Release of NA

• [insert drawing]

Animal Virus Entry

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Step 3. Synthesis

Production of genetic materials

Differs based on genomes

• dsDNA follows tyipcal synthesis

  • Transcription + translation by host

• RNA viruses

  • Virus must carry in or produce the proteins necessary to complete synthesis

Essential genes for viral replication are carried by the virus

DNA Virus Replication

• Goes into host nucleus

RNA Virus Replication

• Viral particle stays in the cytoplasm

• + strand serves as mRNA

Retrovirus Replication

• Goes into the host nucleus

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Step 4. Assembly

• Complex process

• Late proteins are involved

• Baseplate, tail fibers, and head components of bacteriophage T4 are assembled separately

Step 5. Viral Particle Release

Three Mechanisms

• Host cell lysis (naked viruses)

• Exocytosis (naked viruses)

• Budding (enveloped viruses)

• [insert drawing]

6.4 Bacterial and Archaeal Viral Infections

Virulent Phage

• Multiplies immediately upon entering a bacterial host

• Released form host by lytic cycle

Temperate Phage

• Lytic or lysogenic cycle

Lysogenic Conversion

Temperate phage changes phenotype of its host

• Alteration in surface characteristics of the host

  • Bacteria becomes immune to super/re infection

Advantages to lysogeny

• Allows viral NA to stay in the host ('prophage')

Archaeal Viruses

• May be virulent or temperate

• Many establish chronic infections

• Little is known about the mechanisms they use to regulate their replicative cycles

Infection in Eukaryotic cells

Diverse infected conditions

• Acute infection

• Latent infection

• Chronic infection

• Transformation of host cell

The cultivation of Viruses

Virsues can't be cultured like cellular microbes

Plaques

• Cleared area of cellular growth in a lawn of bacterial cells

• Observation of host cell lysis

Cultivation of Animal + Plant Viruses

Animals:

Inoculating suitable host animals or embryonated eggs

• Fertilized chicken eggs incubated for 6-8days after laying

Tissue/cell cultures - on monolayers of animal cells

Cytopathic effects (lysis) can be observed

Plants:

• Plant tissue cultures

• Suitable whole plants

  • Rub mixture of virus + an abrasive

  • May cause localized necrotic lesions or generalized symptoms of infection

Quantification of Virus

Plaque Assays

• Dilutions of virus samples made + plated with appropriate host cells

• Number of plaques counted

• Results expressed as plaque-forming units (PFU)

  • Directly proportional to # of viruses (capable of forming plaques)

Nucleic Acid-Based Subviral Agents: Viroids

• Plant infectious agents

• Small, circular, single-stranded, non-protein coding RNA

• Plant viroids have been targeted by RNA silencing

NA-Based Subviral Agents: Satelliates

• Virus dependent NA

  • DNA or RNA

• Need a helper virus to replicate

• Satelliate viruses encode own capsid proteins

• Most satellites use plant viruses as their helpers

• Satellite viruses (endcode protein) and Satellite NA

Subviral Particles: Prions

Made of only a single protein

Cause a variety of neurodegenerative diseases in humans + animals

• Scrapie in sheep

• Bovine spongiform encephalopathy (BSE) or "mad cow disease"

• Human diseases kuru, fatal familal insomnia, Creutzfeldt-Jakob disease

Current Model of Disease Production by Prions

• PrP^C (prion protein) is present in "normal" form (abnromal form of prion protein is PrP^Sc)

• Conformational change of celluar prion protein (PrP^C) into scrapie prion protein (PrP^Sc)

• PrP^C irreversibly converts to PrP^Sc

• Still unkonwn if the loss of PrP^C or accumulation of PrP^Sc leads to disease

• [insert drawing]