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

Viruses and Prions

Introduction to Viruses

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. Viruses are extremely small, typically ranging from 20–400 nm in size.

• Virology: The scientific study of viruses.

• Obligate intracellular pathogens: Require host cells for replication.

• Acellular: Not composed of cells.

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
Genetic Material	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. They can infect all domains of life, but are commonly classified as bacteriophages (infect bacteria) or animal viruses (infect animals and humans).

• Virion: Single, infectious virus particle.

• Capsid: Protein shell protecting the genome, made of capsomere subunits.

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

Capsid Structures

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

• Helical capsid: Hollow tube-like structure.

• Icosahedral capsid: Three-dimensional polygon.

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

Viral Envelopes

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

• Enveloped viruses: Arise from budding; can be animal viruses.

• Naked viruses: Arise from lysis; all bacteriophages are naked.

Viral Spikes (Peplomers)

Many viruses have spikes (glycoprotein extensions) protruding from the capsid or envelope, which facilitate attachment and entry into host cells. Spikes bind to specific host cell factors.

Influenza viruses mutate frequently, causing changes in spike proteins (antigenic drift and shift). Key spikes include hemagglutinin (HA) and neuraminidase (NA).

Viral Genomes

Viral genomes are compact, typically encoding fewer than 300 genes. They may be DNA or RNA, single or double-stranded, segmented or non-segmented, and circular or linear.

• DNA viruses: Often double-stranded, can be circular or linear.

• RNA viruses: Often single-stranded, can be linear or segmented.

Making mRNA from Viral Genomes

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

• dsDNA viruses: Use host RNA polymerases for transcription.

• ssDNA viruses: Convert to dsDNA before transcription.

• ssRNA+ viruses: Genome acts as mRNA, directly translated.

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

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

• dsRNA viruses: Require viral RNA-dependent RNA polymerase for transcription.

Viral Genome Evolution

Viruses evolve rapidly due to quick replication, high virion production, and frequent mutations, especially in RNA viruses (RNA polymerases lack proofreading). 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

Minor changes in viral antigens (drift) and major genetic reassortments (shift) can lead to new, highly virulent strains, potentially causing pandemics.

Classifying and Naming Viruses

Viruses are classified by the International Committee on Taxonomy of Viruses (ICTV) based on:

• Type of nucleic acid (DNA or RNA)

• Capsid symmetry (helical, icosahedral, complex)

• Envelope presence

• Genome architecture (ssDNA, ssRNA, etc.)

Medically Important Virus Families

Examples of DNA and RNA virus families relevant to human health:

Family	Genome	Capsid	Envelope	Example
Herpesviridae	dsDNA linear	Icosahedral	Enveloped	Herpes simplex virus
Picornaviridae	ssRNA+	Icosahedral	Naked	Poliovirus
Orthomyxoviridae	ssRNA- segmented	Helical	Enveloped	Influenza virus
Retroviridae	ssRNA+ (reverse transcriptase)	Icosahedral	Enveloped	HIV

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). For comparison, a human red blood cell is 8,000 nm in diameter.

Viral Replication Pathways

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

Bacteriophage Replication

Bacteriophages replicate via lytic or lysogenic cycles.

• Lytic cycle: Immediate virion production, host cell lysis.

• Lysogenic cycle: Viral genome integrates into host genome (prophage), replicated with host DNA, can later enter lytic cycle.

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

Animal Virus Replication

Animal viruses follow six steps: attachment, penetration, uncoating, replication, assembly, and release.

• Attachment: Via capsid proteins (naked) or spikes (enveloped).

• Penetration: Enveloped viruses enter by fusion or endocytosis; naked viruses by endocytosis.

• Uncoating: Capsid is digested, genome released.

• Replication: Genome is replicated, viral proteins synthesized.

• Assembly: New virions are formed.

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

Persistent Viral Infections

Some animal viruses cause persistent infections:

• Acute: Immediate virion production.

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

• Latent: Periods of dormancy with intermittent flare-ups (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 of Viruses

Growing Viruses in the Laboratory

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

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

Diagnostic Tests for Viral Infections

Detection methods include:

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

• ELISA: Detects antigens or antibodies via color change.

• Nucleic acid detection: PCR, sequencing, and fluorescent probes for viral genetic material.

Antiviral Drugs

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

• Attachment inhibitors: Maraviroc (HIV), HRIG (rabies).

• Penetration inhibitors: Enfuvirtide (HIV), docosanol (HHV-1).

• Uncoating inhibitors: Amantadine (influenza).

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

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

• Interferons: Signal cells to limit viral entry and replication.

Prions

Prions are infectious proteins that lack genetic material and do not replicate. They cause transmissible spongiform encephalopathies (TSEs), which can be inherited or acquired. Examples include Creuzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Schienker syndrome, and fatal familial insomnia.

• Prion-like neurological disorders: Alzheimer’s, Parkinson’s, ALS—associated with misfolded proteins.

Visual Summary

This summary provides an overview of viral and prion biology, including structure, classification, replication, clinical detection, and treatment strategies, suitable for exam preparation in a college microbiology course.