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 their structure, replication, and metabolic capabilities.

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

• Helical capsid: Hollow tube shape

• Icosahedral capsid: Three-dimensional polygon

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

Viral Envelopes

• Enveloped viruses: Lipid-based envelope surrounds the capsid; arises from budding off the host cell

• Naked viruses: Lack an envelope; arise from lysing the host cell

• Bacteriophages: Always naked

Viral Spikes (Peplomers)

Spikes are glycoprotein extensions that help viruses attach and gain entry to host cells. They bind to specific factors on host cells.

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

Viral Genomes

Viral genomes are compact, usually encoding fewer than 300 genes. They can be DNA or RNA, single or double-stranded, segmented or nonsegmented, circular or linear.

• DNA viral genomes: Often double-stranded, can be circular or linear

• RNA viral genomes: Often single-stranded, can be linear or segmented

Making mRNA from Viral Genomes

• dsDNA viruses: Transcribed using host RNA polymerases

• ssDNA viruses: Converted to dsDNA before transcription

• ssRNA+ viruses: Genome functions 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 into host genome

• dsRNA viruses: Transcribed to make mRNA

Viral Genome Evolution

Viruses change rapidly due to quick replication and high mutation rates, especially in RNA viruses. Mutations can be neutral, beneficial, or deleterious.

• Attenuated strains: Reduced infectivity, used in vaccines

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

Antigenic Drift and Antigenic Shift

• Antigenic drift: Minor changes in viral antigens (e.g., influenza HA and NA spikes)

• Antigenic shift: Major genetic reassortment, can lead to 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)

• Presence or absence of envelope

• Genome architecture (ssDNA, ssRNA, etc.)

Medically Important Virus Families

Host Range and Tropism

Host range is the collection of species a virus can infect. Tropism refers to the tissue or cell specificity, 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. Bacteriophage replication can be lytic or lysogenic.

Lytic Replication Pathway

• Attachment (adsorption)

• Penetration (entry)

• Replication (synthesis)

• Assembly (maturation)

• Release (lysis)

Lysogenic Replication Pathway

• Attachment

• Penetration

• Integration (prophage formation)

• Cell division (prophage copied)

• Stress triggers excision and entry into 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

• Release

Persistent Infections

• Acute infections: Immediate virion production

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

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

Oncogenic Viruses

Oncoviruses can cause cancer by stimulating uncontrolled host cell division or decreasing responsiveness to death signals. Examples include Human papilloma virus (HPV) and Human T-lymphotropic virus (HTLV).

Clinical Aspects of Viruses

Growing Viruses in the Laboratory

• Bacteriophages: Grown using plaque assays

• Animal viruses: Grown in tissue culture, embryonated eggs, or live animal hosts

Diagnostic Tests for Viral Infections

• Detection of viral proteins (antigens) using agglutination tests and ELISA

• Detection of viral genetic material using PCR, sequencing, and fluorescent probes

• Specificity and sensitivity are key for accurate diagnostics

Antiviral Drugs

• Block viral attachment, penetration, uncoating, replication, assembly, or release

• Nucleoside analogs (e.g., acyclovir, ribavirin)

• Reverse transcriptase inhibitors (e.g., AZT)

• Interferons: Signal cells to defend against viral infection

• Oseltamivir and zanamivir: Prevent influenza virion release

Prions

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

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

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

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

Additional info: This summary expands on brief points with academic context, definitions, and examples to provide a comprehensive mini-study guide for Microbiology students.