Viruses and Prions: Structure, Replication, and Pathogenicity

Viruses and Prions

Introduction

Viruses and prions are unique infectious agents studied in microbiology. Unlike prokaryotic and eukaryotic cells, viruses are acellular and require host cells for replication, while prions are infectious proteins. This chapter explores their structure, replication, and impact on human health.

Comparing Viruses, Prokaryotes, and Eukaryotes

Key Differences

Viruses differ fundamentally from cellular life forms such as prokaryotes (bacteria and archaea) and eukaryotes (plants, animals, fungi, protists).

• Cells: Viruses are not cells; prokaryotes and eukaryotes are cellular.

• Living Status: Viruses are not considered alive; prokaryotes and eukaryotes are living organisms.

• Size: Viruses are generally much smaller than prokaryotes and eukaryotes, often requiring electron microscopy for visualization.

• Structure: Viruses have a protein capsid and may have a lipid envelope; prokaryotes and eukaryotes have cell membranes and, in eukaryotes, membrane-bound organelles.

• Replication: Viruses rely on host cell machinery; prokaryotes replicate by binary fission, eukaryotes by mitosis or meiosis.

• Genome Composition: Viral genomes can be DNA or RNA; prokaryotes and eukaryotes have DNA genomes.

Characteristic	Viruses	Prokaryotes	Eukaryotes
Cells?	No	Yes	Yes
Considered alive?	No	Yes	Yes
Relative size	Smaller than prokaryotes	Bigger than viruses	Bigger than prokaryotes and viruses
Filterable?	Yes	Yes (except for some small bacteria)	No
Structure	Protein capsid, possible envelope	Cell wall, membrane	Membrane-bound organelles
Replication	Host cell machinery	Binary fission	Mitosis/Meiosis
Metabolism?	No	Yes	Yes
Genome composition	DNA or RNA	DNA	DNA

Virology: The Study of Viruses

General Properties of Viruses

Virology is the scientific study of viruses. Viruses are submicroscopic, acellular infectious agents that are obligate intracellular pathogens, meaning they must infect a host cell to replicate.

• Extremely small (often 20–300 nm)

• Acellular (not composed of cells)

• Obligate intracellular pathogens

• Over 5,000 mammal-infecting viral species described; ~220 infect humans

• Estimated 320,000 mammalian viruses remain uncharacterized

• About 70% of human-infecting viruses are harbored in other animals (zoonotic potential)

Viral Structure

Virion Components

A virion is a single, infectious virus particle. It consists of:

• Capsid: Protein shell that packages and protects the viral genome. Made of subunits called capsomeres.

• Envelope: Some viruses have a lipid-based envelope derived from the host cell membrane. Enveloped viruses acquire their envelope by budding from the host cell; naked viruses lack an envelope and are released by cell lysis.

• Spikes: Glycoprotein extensions that protrude from the capsid or envelope, facilitating attachment and entry into host cells.

Capsid Shapes:

• Helical: Hollow tube-like structure

• Icosahedral: Three-dimensional polygonal structure

• Complex: Deviations from helical or icosahedral, often seen in bacteriophages

Viral Genomes

Genomic Diversity

Viral genomes are highly variable and can be composed of either DNA or RNA, which may be single-stranded (ss) or double-stranded (ds), linear or circular, and segmented or non-segmented.

• Most viruses have fewer than 300 genes

• Viral genes encode capsomere proteins, enzymes for replication, and structural factors

• Goal: Use host cell machinery to produce viral proteins and assemble new virions

Viral Genome Evolution

Mutation and Reassortment

Viral genomes change rapidly due to:

• Quick replication cycles

• Large numbers of virions produced

• RNA viruses mutate faster than DNA viruses (RNA polymerases lack proofreading)

• Mutations can be neutral, beneficial, or deleterious

• Attenuated strains (with reduced infectivity) are used in vaccines

• Beneficial mutations may allow immune evasion, expanded host range, or increased infectivity

• Reassortment: When two different viral strains infect the same cell, their genomes can mix, creating new strains

Antigenic Drift and Antigenic Shift

Mechanisms of Viral Variation

Antigenic drift and shift are processes by which viruses, especially influenza, change their surface antigens, impacting immune recognition and vaccine effectiveness.

• Antigenic Drift: Minor changes in viral antigens due to frequent mutations in the RNA genome, leading to gradual changes in viral spikes.

• Antigenic Shift: Major genetic reassortment resulting in new viral strains with significantly altered antigens, often leading to pandemics due to lack of population immunity.

Example: Influenza virus undergoes both drift and shift, complicating vaccine design and effectiveness.

Bacteriophage Replication

Lytic and Lysogenic Cycles

Bacteriophages are viruses that infect bacteria. They can replicate via two main pathways:

• Lytic Cycle: Phage infects the host, immediately produces new virions, and lyses the cell to release progeny.

• Lysogenic Cycle: Phage genome integrates into the host genome as a prophage, replicates with the host cell, and can later enter the lytic cycle upon stress.

Lytic Cycle Steps:

1. Attachment (adsorption)

2. Penetration (entry)

3. Replication (synthesis)

4. Assembly (maturation)

5. Release (lysis)

Lysogenic Cycle:

• Phage genome integrates into host DNA (prophage)

• Prophage is copied during cell division

• Can confer new pathogenic properties (phage conversion), e.g., toxin production in Corynebacterium diphtheriae and Clostridium botulinum

Animal Virus Replication

Generalized Replication Pathway

Animal viruses replicate through six main steps:

1. Attachment

2. Penetration (entry): Enveloped viruses enter via endocytosis or membrane fusion; naked viruses enter by endocytosis

3. Uncoating: Capsid is digested by host enzymes

4. Replication (synthesis): Genome is replicated and viral proteins are produced

5. Assembly: New virions are formed

6. Release: Virions exit the cell (budding for enveloped viruses, lysis for naked viruses)

Persistent Infections

Chronic and Latent Infections

Some animal viruses cause persistent infections, which can be chronic or latent.

• Acute Infection: Rapid onset, production of new virions, and clearance by the immune system

• Persistent Infection: Virus remains in the host, evading immune clearance

• Chronic Infection: Slow progression, continuous production of virus (e.g., HIV)

• Latent Infection: Periods of dormancy interrupted by flare-ups (e.g., Herpesviridae family: HSV-1, HSV-2, varicella-zoster virus)

Oncogenic Viruses

Viruses and Cancer

Oncogenic viruses (oncoviruses) can cause cancer by stimulating uncontrolled cell division or inhibiting cell death signals.

• Responsible for 10–15% of human cancers

• Examples: Human papillomavirus (HPV), Human T-lymphotropic virus (HTLV)

Antiviral Drugs and Vaccines

Managing Viral Infections

Antiviral drugs target various steps in the viral replication pathway but rarely cure infections; they typically limit viral spread.

• Viruses are obligate intracellular pathogens, making selective toxicity challenging

• Fewer drug targets compared to cellular pathogens

• Vaccines are highly effective for prevention, training the immune system to recognize viral antigens

• Drug targets include attachment, penetration, and uncoating steps

Prions: Non-cellular Infectious Agents

Characteristics and Diseases

Prions are infectious proteins that do not contain nucleic acids and do not replicate like viruses. They cause transmissible spongiform encephalopathies (TSEs), which are fatal neurodegenerative diseases.

• Prions: Misfolded proteins that induce abnormal folding in normal proteins

• Diseases: Creutzfeldt-Jakob disease (CJD), Bovine Spongiform Encephalopathy (BSE, "Mad Cow" disease), Gerstmann-Sträussler-Scheinker syndrome

• Transmission can occur via contaminated food, medical instruments, or inherited mutations

Key Terms and Concepts

• Virion: Complete, infectious virus particle

• Capsid: Protein shell of a virus

• Envelope: Lipid membrane surrounding some viruses

• Spikes: Glycoprotein projections for host cell attachment

• Antigenic Drift: Minor antigenic changes due to mutation

• Antigenic Shift: Major antigenic changes due to reassortment

• Prophage: Phage genome integrated into bacterial DNA

• Oncogenic Virus: Virus capable of causing cancer

• Prion: Infectious protein causing neurodegenerative disease

Formulas and Equations

Viral Replication Rate

$\text{Rate of viral replication} = k[\text{Host cell factors}]$

Mutation Rate Comparison

$\text{Mutation rate}_{\text{RNA virus}} > \text{Mutation rate}_{\text{DNA virus}}$

Antigenic Shift (Reassortment)

$\text{New strain} = \text{Genome}_{\text{Virus A}} + \text{Genome}_{\text{Virus B}}$

Additional info:

• Tables and some content were inferred and expanded for clarity and completeness.

• Scientific names are italicized according to academic convention.