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

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

Viruses: Nonliving Pathogens

Viruses are acellular, submicroscopic infectious agents that require a host cell for replication. They are obligate intracellular pathogens and are studied in the field of virology. Over 5,000 mammal-infecting viral species have been described, with many more uncharacterized. Most viruses that infect humans are harbored in other animals.

• Size: Extremely small (20–400 nm)

• Acellular: Lack cellular structure

• Obligate Intracellular Pathogens: Require host cells to replicate

Comparing Viruses, Prokaryotes, and Eukaryotes

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

Feature	Viruses	Prokaryotes	Eukaryotes
Cellular Structure	No	Yes	Yes
Genome	DNA or RNA	DNA	DNA
Replication	Host-dependent	Binary fission	Mitosis/meiosis
Metabolism	None	Present	Present

Viral Structure and Genomic Features

Viruses can infect all domains of life. The two main types discussed are bacteriophages (infect bacteria) and animal viruses (infect animals and humans).

• Virion: Single, infectious virus particle

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

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

Enveloped viruses have a lipid-based envelope derived from the host cell membrane. Naked viruses lack an envelope and arise from lysing the host cell.

• Animal viruses: May be enveloped or naked

• Bacteriophages: Always naked

Viral Spikes (Peplomers)

Spikes are glycoprotein extensions that facilitate attachment and entry into host cells. They bind to specific host cell factors.

• Influenza A spikes: Hemagglutinin (HA) and Neuraminidase (NA)

Viral Genomes

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

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

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; requires RNA-dependent RNA polymerase

• Retroviruses: RNA genome converted to DNA by reverse transcriptase

• dsRNA viruses: Require RNA-dependent RNA polymerase

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

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

Antigenic Drift and Shift

Influenza viruses undergo antigenic drift (minor changes) and antigenic shift (major reassortment), affecting HA and NA spikes. Antigenic shift can lead to pandemics due to lack of immune protection.

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

DNA and RNA virus families are classified by genome type, capsid shape, and envelope presence. Examples include:

• DNA viruses: Papillomaviridae, Parvoviridae, Adenoviridae, Hepadnaviridae, Poxviridae, Herpesviridae

• RNA viruses: 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 tissue or cell specificity, determined by viral surface factors.

• Broad tropism: Infects multiple cell types

• Narrow tropism: Infects specific cell types

Virus Sizes

Viruses vary in size from 30 nm (rhinovirus, poliovirus) to 1,500 nm (pithovirus). For comparison, human red blood cells are 8,000 nm in diameter.

Viral Taxonomy and Naming

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

Viral Replication Pathways

Viruses hijack host cell machinery to multiply. Bacteriophage replication can be lytic or lysogenic.

Lytic Replication Pathway

Viruses immediately build new virions and kill the host cell.

• Attachment

• Penetration

• Replication

• Assembly

• Release

Lysogenic Replication Pathway

Temperate phages incorporate their genome into the host cell, forming a prophage. The prophage is copied as the cell divides and may excise itself under stress to enter the lytic cycle.

Phage Conversion

Prophages can confer new pathogenic properties to bacteria, such as toxin production (e.g., Corynebacterium diphtheriae, Clostridium botulinum).

Animal Virus Replication

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

• Attachment: Naked viruses use capsid proteins; enveloped viruses use spikes

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

• Uncoating: Capsid is digested, genome released

• Replication: Genome is replicated, proteins synthesized

• Assembly: New virions formed

• Release: Enveloped viruses released by budding; naked viruses by cell lysis

Persistent Infections

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

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

• Latent: Flare-ups with periods of dormancy (e.g., Herpesviridae family)

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, where clear zones (plaques) indicate lysed cells.

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

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 agglutination

• ELISA: Detects antigens or antibodies via color change

• Nucleic acid detection: PCR, sequencing, fluorescent probes

Antiviral Drugs

Antiviral drugs target various steps in viral replication, but rarely cure infections. Vaccines are crucial for prevention.

• Attachment blockers: HRIG (Rabies), Maraviroc (HIV)

• Penetration blockers: Interferon-alfa, Enfuvirtide, Docosanol, Palivizumab

• Uncoating blockers: Amantadine, Rimantadine, Vapendavir

• Replication blockers: Nucleoside analogs (Acyclovir, Ribavirin), NRTIs (AZT)

• Release blockers: Oseltamivir (Tamiflu), Zanamivir (Relenza)

Prions

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

• Inherited TSEs: Gerstmann-Straussler-Schienker syndrome, Fatal familial insomnia

• Acquired TSEs: Creuzfeldt-Jakob disease (CJD), variant CJD, sporadic, iatrogenic

Some neurodegenerative diseases (Alzheimer's, Parkinson's, ALS) exhibit prion-like features due to misfolded proteins.

Visual Summary: Viruses and Prions

Additional info: Tables and figures were recreated and expanded for clarity. All key terms and concepts were defined and explained for exam preparation.