Viruses and Prions: Structure, Classification, Replication, and Disease

Viruses and Prions

What Are Viruses?

Viruses are unique infectious agents that differ fundamentally from living organisms. They are acellular, nonliving entities that require a host cell for replication and metabolic activities.

• Virion: A single virus particle, consisting of genetic material (DNA or RNA) enclosed within a protein capsid.

• Acellular and Obligate Intracellular Pathogens: Viruses cannot reproduce or carry out metabolism independently; they must infect living cells.

• Diversity: Over 5,000 mammal-infecting viral species are described; approximately 220 infect humans, with many more uncharacterized.

Structure and Classification

Viruses exhibit diverse structural features and are classified based on several criteria.

• Capsid: The protein shell made of capsomeres; shapes include helical, icosahedral, or complex.

• Envelope: Some viruses possess a lipid envelope derived from the host cell membrane (enveloped viruses); others lack this feature (naked viruses).

• Spikes (Peplomers): Glycoprotein extensions that facilitate attachment to host cells (e.g., influenza's HA and NA spikes).

• Genome: Can be DNA or RNA, single- or double-stranded, linear or circular, segmented or nonsegmented; most viral genomes contain fewer than 300 genes.

• Classification: Based on nucleic acid type, capsid symmetry, envelope presence, and genome architecture. The Baltimore classification groups viruses by genome type and replication method.

• Taxonomy: Highest rank is order (ends in -virales), followed by family (-viridae), subfamily (-virinae), genus (-virus), and species.

Example: Influenza Virus Structure

• Enveloped virus with helical capsid.

• Contains RNA genome.

• Has HA (hemagglutinin) and NA (neuraminidase) spikes for host cell attachment and release.

Viral Replication

Viruses replicate by hijacking host cell machinery. The process varies between animal viruses and bacteriophages.

• General Steps (Animal Viruses): Attachment, penetration, uncoating, replication, assembly, release.

• Bacteriophage Replication:

  • Lytic Cycle: Virus immediately replicates and lyses host cell.

  • Lysogenic Cycle: Viral genome integrates into host DNA as a prophage; can later enter lytic cycle.

  • Phage Conversion: Prophage may confer new traits (e.g., toxin genes) to bacteria.

• Animal Virus Replication: Entry can occur by fusion or endocytosis; release by budding (enveloped viruses) or lysis (naked viruses).

Example: HIV Replication

• Attachment via CD4 receptor.

• Fusion with host membrane.

• Reverse transcription of RNA genome.

• Integration into host DNA.

• Assembly and budding from host cell.

Viral Genomic Change and Evolution

Viruses evolve rapidly due to high mutation rates and genetic reassortment.

• High Mutation Rates: Especially in RNA viruses, as RNA polymerases lack proofreading ability.

• Antigenic Drift: Minor changes from frequent mutations (e.g., flu virus spike proteins).

• Antigenic Shift: Major changes from reassortment between different viral strains, potentially leading to pandemics.

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

Example: Influenza Pandemics

• Antigenic shift in influenza A can produce new subtypes, causing global outbreaks.

Infection Types

Viral infections can be classified based on their duration and effects on the host.

• Acute Infections: Rapid onset, typically cleared by the immune system.

• Persistent Infections: Virus remains in host; can be chronic (continuous production) or latent (periods of dormancy and flare-ups).

• Oncogenic Viruses (Oncoviruses): Some viruses cause cancer by integrating into host DNA or altering cell regulation (e.g., HPV, HTLV, EBV).

Detection and Cultivation

Viruses are detected and cultivated using specialized methods.

• Bacteriophages: Grown using plaque assays; clear zones (plaques) indicate viral lysis of bacteria.

• Animal Viruses: Grown in tissue culture or live animals.

• Diagnostic Tests:

  • Antigen/Antibody Tests: Detect viral proteins or host antibodies (e.g., agglutination, ELISA).

  • Molecular Tests: Detect viral DNA/RNA; specificity (no false positives) and sensitivity (no false negatives) are key.

Example: ELISA Test

• Used to detect HIV antibodies in patient serum.

Antiviral Drugs

Antiviral drugs are designed to inhibit various steps in viral replication, but most limit spread rather than cure infections.

• Targets: Attachment, penetration, uncoating, reverse transcription, etc.

• Effect: Most drugs limit viral spread; few are curative.

Example: Oseltamivir (Tamiflu)

• Inhibits neuraminidase in influenza virus, preventing release of new virions.

Prions

Prions are infectious proteins that cause severe neurodegenerative diseases.

• Definition: Prions are infectious proteins with no genetic material.

• Diseases: Cause transmissible spongiform encephalopathies (TSEs), such as Creutzfeldt-Jakob disease and Kuru.

• Mechanism: Induce abnormal folding and aggregation of normal proteins in nervous tissue, leading to neurodegeneration.

Example: Mad Cow Disease (Bovine Spongiform Encephalopathy)

• Caused by prion infection in cattle; can be transmitted to humans as variant Creutzfeldt-Jakob disease.

Summary Table: Virus Classification Criteria

Criterion	Description	Example
Nucleic Acid Type	DNA or RNA; single- or double-stranded	HIV (ssRNA), Herpesvirus (dsDNA)
Capsid Symmetry	Helical, icosahedral, or complex	Influenza (helical), Adenovirus (icosahedral)
Envelope Presence	Enveloped or naked	Influenza (enveloped), Poliovirus (naked)
Genome Architecture	Linear, circular, segmented, or nonsegmented	Influenza (segmented), Papillomavirus (circular)

Key Equations and Concepts

• Mutation Rate in RNA Viruses:

$\text{Mutation Rate} = \frac{\text{Number of Mutations}}{\text{Genome Size} \times \text{Replication Cycles}}$

• Specificity and Sensitivity in Diagnostic Tests:

$\text{Specificity} = \frac{\text{True Negatives}}{\text{True Negatives} + \text{False Positives}}$

$\text{Sensitivity} = \frac{\text{True Positives}}{\text{True Positives} + \text{False Negatives}}$