Viruses and Prions: Structure, Replication, and Clinical Relevance

Viruses and Prions

Introduction to Viruses

Viruses are submicroscopic, acellular infectious agents that require a host cell for replication. The study of viruses is known as virology. Viruses can infect all forms of life, including bacteria (bacteriophages), animals, and plants. They are considered nonliving because they lack cellular structure and metabolism.

• Size: Typically 20–400 nm, much smaller than prokaryotic and eukaryotic cells.

• Obligate intracellular pathogens: Cannot reproduce outside a host cell.

• Host range: Viruses can infect every branch in the tree of life.

Comparison of Viruses, Prokaryotes, and Eukaryotes

Viruses differ fundamentally from prokaryotic and eukaryotic cells in structure, replication, and metabolism.

Characteristic	Viruses	Prokaryotes	Eukaryotes
Cells?	No	Yes	Yes
Considered alive?	No	Yes	Yes
Relative size	Smaller than prokaryotes	Bigger than viruses, smaller than eukaryotes	Bigger than prokaryotes and viruses
Structure	Protein capsid, nucleic acid	Cells without nuclei	Cells with nuclei
Replication	Hijack host machinery	Binary fission	Mitosis/Meiosis
Metabolism	No	Yes	Yes
Genome	DNA or RNA	DNA	DNA

Viral Structure and Genomic Features

Virion Structure

A virion is a single, infectious virus particle. It consists of a protective protein shell called a capsid, which encloses the viral genome (either DNA or RNA). Some viruses also possess an outer lipid envelope derived from the host cell membrane.

• Capsid: Made of protein subunits called capsomeres.

• Envelope: Lipid-based, present in some animal viruses.

Capsid Symmetry

• Helical capsids: Hollow tube-like structure (e.g., tobacco mosaic virus).

• Icosahedral capsids: Three-dimensional polygons (e.g., adenovirus, coronavirus).

• Complex capsids: More elaborate structures, often seen in bacteriophages.

Viral Envelopes and Spikes

Enveloped viruses have a lipid membrane surrounding the capsid, acquired from the host cell during budding. Naked viruses lack this envelope and are released by cell lysis. Many viruses have surface proteins called spikes (peplomers) that facilitate attachment to host cells.

• Enveloped viruses: e.g., influenza, herpes, coronaviruses.

• Naked viruses: e.g., poliovirus, human papillomavirus.

• Bacteriophages: Always naked, released by lysis.

Viral Genomes

Viral genomes are highly diverse and can be composed of DNA or RNA, which may be single- or double-stranded, linear, circular, or segmented. Most viruses have fewer than 300 genes, encoding structural proteins, enzymes for replication, and other factors.

• Genome types: dsDNA, ssDNA, dsRNA, ssRNA (positive or negative sense).

• Segmented genomes: Genome divided into separate pieces (e.g., influenza virus).

Viral Replication and Mutation

Viruses replicate rapidly and produce large numbers of progeny, especially RNA viruses, which have high mutation rates due to lack of proofreading by RNA polymerases. This leads to rapid evolution and emergence of new strains.

• Mutation effects: Neutral, beneficial, or detrimental.

• Attenuated strains: Weakened viruses used in vaccines.

• Reassortment: Exchange of genome segments between different viral strains infecting the same cell, leading to new combinations.

Antigenic Drift and Shift

Influenza viruses are notable for frequent changes in their surface antigens (spikes), which can occur by two mechanisms:

• Antigenic drift: Minor changes due to point mutations in HA and NA spikes, leading to seasonal epidemics.

• Antigenic shift: Major genetic reassortment, often resulting in new, highly infectious strains and pandemics.

Classification and Naming of Viruses

Classification Criteria

Viruses are classified based on:

1. Type of nucleic acid (DNA or RNA)

2. Capsid symmetry (helical, icosahedral, complex)

3. Presence or absence of an envelope

4. Genome architecture (e.g., ssDNA, dsRNA)

Naming Conventions

Taxon	Example	Notes
Order	Herpesvirales	Ends in 'virales'
Family	Herpesviridae	Ends in 'viridae'
Subfamily	Alphaherpesvirinae	Ends in 'virinae'
Genus	Simplexvirus	Ends in 'virus'
Species	Human herpesvirus-1	Not abbreviated

Host Range and Tropism

Host Range

The host range of a virus is the spectrum of species it can infect. Some viruses are species-specific, while others can infect multiple species due to genetic changes or reassortment.

• Example: Measles virus infects only humans; avian influenza can infect birds and, after reassortment, humans.

Tropism

Tropism refers to the specificity of a virus for particular host tissues or cell types, determined by viral surface proteins and host cell receptors.

• Broad tropism: Ebola virus infects many cell types.

• Narrow tropism: Hepatitis viruses infect primarily liver cells.

Viral Replication

Bacteriophage Replication

Bacteriophages infect bacteria and replicate via two main pathways: lytic and lysogenic cycles.

• Lytic cycle: Virus immediately replicates, lyses host cell, and releases new virions.

• Lysogenic cycle: Viral genome integrates into host DNA as a prophage, replicates with host, can later enter lytic cycle.

• Phage conversion: Prophages can confer new pathogenic traits to bacteria (e.g., toxin production in Corynebacterium diphtheriae and Clostridium botulinum).

Animal Virus Replication

Animal viruses follow a generalized replication cycle with six main steps:

1. Attachment: Virus binds to host cell receptors via capsid proteins or spikes.

2. Penetration: Entry by endocytosis or membrane fusion.

3. Uncoating: Capsid is removed, releasing viral genome.

4. Replication (Synthesis): Genome is replicated, viral proteins are synthesized.

5. Assembly: New virions are assembled.

6. Release: Enveloped viruses bud off; naked viruses lyse the host cell.

Persistent Viral Infections and Oncogenesis

Types of Persistent Infections

• Acute infections: Rapid onset, short duration (e.g., influenza).

• Chronic infections: Continuous release of virions, slow disease progression (e.g., HIV).

• Latent infections: Periods of dormancy with intermittent flare-ups (e.g., herpesviruses).

Oncogenic Viruses

Some viruses can cause cancer by integrating into the host genome or inducing chronic inflammation, leading to uncontrolled cell division.

Virus	Genome	Integrates?	Cancer Link	Mechanism
HPV	DNA	Yes	Cervical, oropharyngeal, anal cancers	Uncontrolled cell division
HHV-8	DNA	No	Kaposi sarcoma	Uncontrolled cell division
EBV	DNA	No	Lymphomas, Hodgkin’s disease	Uncontrolled cell division
HTLV	RNA	Yes	Adult T-cell leukemia	Uncontrolled cell division
Hepatitis B	DNA	No	Liver cancer	Chronic inflammation
Hepatitis C	RNA	No	Liver cancer	Chronic inflammation

Virus Detection and Cultivation

Plaque Assays

Plaque assays are used to quantify bacteriophages. Each clear zone (plaque) on a bacterial lawn represents lysis by a single phage. The number of plaque-forming units (PFUs) indicates viral titer.

Growing Animal Viruses

Animal viruses are cultivated in tissue cultures, embryonated eggs, or live animal hosts. Tissue culture is the most common method for laboratory propagation.

Diagnostic Methods

• Latex agglutination tests: Detect viral antigens or antibodies using latex beads.

• ELISA: Enzyme-linked immunosorbent assay for detecting viral proteins or antibodies.

• Nucleic acid detection: PCR, sequencing, and fluorescent probes for viral DNA/RNA.

Key test qualities: Specificity (no false positives) and sensitivity (no false negatives).

Antiviral Drugs and Vaccines

Antiviral Drug Mechanisms

• Entry inhibitors: Block viral attachment or penetration (e.g., docosanol, palivizumab).

• Nucleoside analogs: Mimic nucleotides, inhibit viral genome replication (e.g., acyclovir, ribavirin).

• Reverse transcriptase inhibitors: Block retroviral replication (e.g., AZT).

• Antisense antivirals: Bind viral RNA, prevent translation (e.g., Vitravene).

• Interferons: Signal uninfected cells to mount antiviral defenses.

• Neuraminidase inhibitors: Prevent influenza virion release (e.g., oseltamivir).

Most antivirals limit, but do not cure, infections. Vaccination is crucial for prevention.

Prions

Prion Diseases

Prions are infectious proteins that lack nucleic acids. They cause transmissible spongiform encephalopathies (TSEs), which are fatal neurodegenerative diseases. Prions induce misfolding of normal proteins in the brain, leading to tissue degeneration and characteristic sponge-like holes.

• Examples: Creutzfeldt-Jakob disease, mad cow disease.

• Diagnosis: Detection of spongiform changes in brain tissue post-mortem.

Prion-like Mechanisms in Neurodegenerative Diseases

Some neurodegenerative diseases, such as Alzheimer's, Parkinson's, and ALS, exhibit prion-like mechanisms, where misfolded proteins propagate by inducing misfolding in normal proteins. However, these are not true prion diseases.