Viruses and Prions: Structure, Classification, Replication, and Clinical Aspects

Viruses and Prions: Structure, Classification, Replication, and Clinical Aspects

Viruses: Basic Properties

Viruses are nonliving pathogens that infect a wide range of hosts, including humans and other mammals. They are acellular and obligate intracellular pathogens, meaning they require a host cell to replicate. The study of viruses is known as virology.

• Size: Extremely small (20–400 nm)

• Structure: Submicroscopic, infectious agents

• Host Range: Over 5,000 mammal-infecting viral species described; many remain uncharacterized

Comparing Viruses, Prokaryotes, and Eukaryotes

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

Feature	Viruses	Prokaryotes	Eukaryotes
Cellular Structure	Acellular	Cellular	Cellular
Genome	DNA or RNA	DNA	DNA
Replication	Host-dependent	Binary fission	Mitosis/meiosis
Metabolism	None	Present	Present

Viral Structure and Genomic Features

Viruses exhibit diverse structural and genomic features, allowing them to infect every branch of the tree of life. The two main types are bacteriophages (infect bacteria) and animal viruses (infect animals and humans).

• Virion: Single, infectious virus particle

• Capsid: Protein shell that packages and protects the genome; made of capsomere subunits

• Genome: DNA or RNA, single or double-stranded, circular or linear, segmented or nonsegmented

Capsid Structures

Most animal viruses have either helical or icosahedral capsids. Deviations are classified as complex capsids.

• Helical capsid: Hollow tube shape

• Icosahedral capsid: Three-dimensional polygon

• Complex capsid: Found in bacteriophages, often with additional structures for genome injection

Viral Envelopes

Some viruses have a lipid-based envelope surrounding the capsid, acquired from the host cell membrane during budding. Naked viruses lack an envelope and are released by lysing the host cell.

• Animal viruses: May be enveloped or naked

• Bacteriophages: Always naked

Viral Spikes (Peplomers)

Many viruses possess spikes (glycoprotein extensions) that protrude from the capsid or envelope, facilitating attachment and entry into host cells. Spikes bind to specific host cell factors.

Influenza viruses frequently mutate their spike proteins, leading to antigenic drift and shift. The main spikes are hemagglutinin (HA) and neuraminidase (NA).

Viral Genomes

Viral genomes are compact, typically encoding fewer than 300 genes. They direct the synthesis of viral proteins and replication enzymes.

• Types: DNA or RNA; single or double-stranded; circular or linear; segmented or nonsegmented

• Goal: Get host cell to make viral proteins and assemble new virions

Making mRNA from Viral Genomes

Viruses use various strategies to produce mRNA for protein synthesis, depending on their genome type.

• dsDNA viruses: Transcribed by host RNA polymerases

• ssDNA viruses: Converted to dsDNA before transcription

• ssRNA+ viruses: Genome acts as mRNA

• ssRNA- viruses: Genome is complementary to mRNA; transcribed by viral RNA-dependent RNA polymerases

• Retroviruses: RNA genome converted to DNA by reverse transcriptase, then integrated and transcribed

• dsRNA viruses: Transcribed to make mRNA

Viral Genome Evolution

Viruses mutate rapidly due to quick replication and lack of proofreading in RNA polymerases. Mutations can be neutral, beneficial, or deleterious.

• Attenuated strains: Reduced infectivity, used in vaccines

• Beneficial mutations: May increase infectivity, broaden host range, or expand tropism

• Reassortment: Occurs when two viral strains coinfect a cell, leading to new strains

Antigenic Drift and Shift

Influenza viruses undergo antigenic drift (minor changes in HA and NA spikes) and antigenic shift (major genetic reassortment), which can lead to pandemics.

Classifying and Naming Viruses

The International Committee on Taxonomy of Viruses (ICTV) classifies viruses based on:

• Type of nucleic acid (DNA or RNA)

• Capsid symmetry (helical, icosahedral, complex)

• Presence or absence of envelope

• Genome architecture (ssDNA, ssRNA, etc.)

Medically Important Virus Families

Viruses are grouped into families based on genome type, capsid shape, and envelope status. Examples include:

• DNA virus families: Papillomaviridae, Parvoviridae, Adenoviridae, Hepadnaviridae, Poxviridae, Herpesviridae

• RNA virus families: Calciviridae, Picornaviridae, Paramyxoviridae, Filoviridae, Rhabdoviridae, Bunyaviridae, Orthomyxoviridae, Arenaviridae, Flaviviridae, Retroviridae, Togaviridae, Reoviridae, Coronaviridae

Host Range and Tropism

Host range is the collection of species a virus can infect. Tropism refers to the specific tissues or cells a virus targets, determined by viral surface factors.

• Broad tropism: Infects multiple cell types

• Narrow tropism: Infects only one cell type

Virus Sizes

Viruses vary greatly in size, from 30 nm (rhinovirus, poliovirus) to 1,500 nm (pithovirus).

Viral Replication Pathways

Viruses hijack host cell machinery to multiply. Bacteriophages and animal viruses have distinct replication pathways.

Bacteriophage Replication

• Lytic pathway: Immediate virion production, host cell lysis

• Lysogenic pathway: Viral genome integrates into host genome as a prophage, replicated with host DNA

• Phage conversion: Prophages confer new pathogenic properties (e.g., toxin production)

Animal Virus Replication

Animal virus replication involves six steps: attachment, penetration, uncoating, replication, assembly, and release.

Persistent Viral Infections

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

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

• Latent: Intermittent flare-ups with dormancy (e.g., herpesviruses)

Oncogenic Viruses

Oncogenic viruses (oncoviruses) can cause cancer by stimulating uncontrolled cell division or reducing cell death signals. Examples include human papilloma viruses (HPVs) and human T-lymphotropic viruses (HTLV).

Clinical Aspects: Laboratory Growth and Detection

Viruses require host cells for laboratory growth. Bacteriophages are grown using plaque assays, while animal viruses may require tissue culture or embryonated eggs.

Diagnostic Tests

Detection methods include searching for viral proteins (antigens), viral genetic material, or patient antibodies.

• Agglutination tests: Use antibodies or antigens linked to beads; positive result is bead clumping

Antiviral Drugs

Antiviral drugs target various steps in viral replication, including attachment, penetration, uncoating, replication, assembly, and release. Most drugs limit infection rather than cure it.

• Nucleoside analogs: Block replication (e.g., acyclovir, ribavirin)

• Reverse transcriptase inhibitors: Target retroviruses (e.g., AZT)

• Protease inhibitors: Block viral protein processing

• Interferons: Signal cells to defend against viral entry and replication

• Release inhibitors: Prevent budding (e.g., oseltamivir, zanamivir)

Prions

Prions are infectious proteins that cause transmissible spongiform encephalopathies (TSEs). They do not contain genetic material and do not replicate like viruses.

• Diseases: Creuzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Schienker syndrome, fatal familial insomnia

• Transmission: Inherited, sporadic, iatrogenic, variant

• Prion-like disorders: Alzheimer’s, Parkinson’s, ALS (due to misfolded proteins)

Visual Summary

Additional info: These notes expand on brief points with academic context, definitions, and examples to provide a comprehensive, exam-ready guide for Microbiology students.