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

Viruses and Prions: Basic Principles

Viruses as Nonliving Pathogens

Viruses are acellular, obligate intracellular pathogens that infect all branches of life, including humans and animals. They are extremely small (20–400 nm) and require host cells to replicate. The study of viruses is called virology.

• Viruses are submicroscopic infectious agents.

• Over 5,000 mammal-infecting viral species have been described, with many more uncharacterized.

• Many human-infecting viruses are harbored in other animals.

Comparison of 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
Size	20–400 nm	0.5–5 μm	10–100 μm

Viral Structure and Genomic Features

Virion and Capsid

A virion is a single, infectious virus particle. It consists of a protective protein capsid that packages the viral genome (DNA or RNA). Capsids are made of capsomere subunits and account for most of the virion's mass.

• Capsids can be helical, icosahedral, or complex.

• Helical capsids resemble hollow tubes; icosahedral capsids are three-dimensional polygons; complex capsids are seen in bacteriophages.

Viral Envelopes

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

• Animal viruses may be enveloped or naked.

• Bacteriophages are always naked.

Viral Spikes (Peplomers)

Many viruses have spikes (peplomers), which are glycoprotein extensions that facilitate attachment and entry into host cells. These spikes bind to specific host cell factors.

• Influenza viruses have hemagglutinin (HA) and neuraminidase (NA) spikes, which frequently mutate.

Viral Genomes

Viral genomes are highly diverse and typically contain fewer than 300 genes. They encode capsomere proteins, replication enzymes, and structural factors.

• Genomes may be DNA or RNA, single- or double-stranded, segmented or nonsegmented, circular or linear.

The goal of all viruses is to use the host cell to produce viral proteins and assemble new virions.

Viral Genome Replication Strategies

Viruses use various strategies to generate 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, directly translated.

• ssRNA- viruses: Genome is complementary to mRNA; requires RNA-dependent RNA polymerase.

• Retroviruses: ssRNA genome is reverse transcribed to DNA, which integrates into the host genome.

• dsRNA viruses: Transcribed to make mRNA using viral RNA-dependent RNA polymerases.

Viral Evolution and Genetic Change

Mutation and Reassortment

Viruses evolve rapidly due to quick replication, large numbers of virions, and high mutation rates, especially in RNA viruses (RNA polymerases lack proofreading).

• Mutations can be neutral, beneficial, or deleterious.

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

• Reassortment occurs when two viral strains coinfect a cell, producing new genetic combinations.

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 due to lack of immune protection.

Classification and Naming of Viruses

Criteria for Classification

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, dsRNA, etc.)

Medically Important Viral Families

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

• DNA virus families: Papillomaviridae (HPV), 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 specificity for certain tissues or cell types, determined by viral surface factors.

• Measles virus infects only humans (narrow host range).

• Some viruses have broad tropism, infecting multiple cell types.

Virus Sizes

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

Naming Conventions

Viruses are not assigned to domains or kingdoms. The highest taxon is phylum, followed by order, family, genus, and species.

Viral Replication Pathways

Bacteriophage Replication: Lytic and Lysogenic Cycles

Bacteriophages replicate via two main pathways:

• Lytic cycle: Immediate production of new virions, host cell is lysed.

• Lysogenic cycle: Phage genome integrates into host genome as a prophage, replicated with host DNA; can later enter lytic cycle.

Phage conversion occurs when prophages confer new pathogenic properties to bacteria (e.g., toxin production).

Animal Virus Replication

Animal viruses replicate in six steps:

1. Attachment

2. Penetration

3. Uncoating

4. Replication

5. Assembly

6. Release

Enveloped viruses enter by fusion or endocytosis; naked viruses enter by endocytosis. Uncoating releases the viral genome.

Persistent Infections

Some animal viruses cause persistent infections:

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

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

Oncogenic Viruses

Oncogenic viruses (oncoviruses) can cause cancer by stimulating uncontrolled cell division or reducing cell death signals. Examples include HPV and HTLV.

Clinical Aspects of Viruses

Laboratory Growth of Viruses

Viruses require host cells for laboratory cultivation. Bacteriophages are grown using plaque assays on petri plates, where clear zones (plaques) indicate lysed cells.

Animal viruses are grown in tissue culture, embryonated eggs, or live animal hosts.

Diagnostic Tests for Viral Infections

Detection methods include:

• Searching for viral proteins (antigens) using purified antibodies.

• Agglutination tests: Antibodies or antigens linked to latex beads; agglutination indicates positive result.

• Enzyme-linked immunosorbent assays (ELISA): Detect antigens or antibodies via color change.

• Nucleic acid detection (PCR, sequencing, fluorescent probes): Highly sensitive and specific.

Antiviral Drugs

Antiviral drugs target various steps in viral replication, but typically limit rather than cure infections. Vaccines are crucial for prevention.

• Attachment, penetration, and uncoating inhibitors: e.g., amantadine, rimantadine, maraviroc, docosanol.

• Replication inhibitors: Nucleoside analogs (acyclovir, ribavirin), NRTIs (AZT), antisense antivirals (vitravene).

• Release inhibitors: Oseltamivir (Tamiflu), zanamivir (Relenza).

• Interferons: Signal cells to make defensive changes.

Prions

Prions and Spongiform Encephalopathies

Prions are infectious proteins with no genetic material. They cause transmissible spongiform encephalopathies (TSEs), which can be inherited or acquired (e.g., Creuzfeldt-Jakob disease).

• Prions do not replicate but induce misfolding of normal proteins.

• Some neurodegenerative diseases (Alzheimer's, Parkinson's, ALS) exhibit prion-like features.

Additional info: This guide expands on brief points with academic context, definitions, and examples to ensure completeness and clarity for exam preparation.