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

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Microbes: Living and Nonliving Agents Studied in Microbiology

Overview of Microbial Classes

Microbiology encompasses the study of both living and nonliving agents, including bacteria, archaea, protists, fungi, helminths, viruses, and prions. Each class has distinct structural and functional characteristics.

Microbe	Cell Type	Notes
Bacteria	Prokaryotic	Unicellular; pathogenic and nonpathogenic
Archaea	Prokaryotic	Unicellular; nonpathogenic; most live in extreme environments
Protists	Eukaryotic	Unicellular and multicellular; pathogenic and nonpathogenic (e.g., amoebae, algae)
Fungi	Eukaryotic	Unicellular (yeast) and multicellular (mushrooms); pathogenic and nonpathogenic
Helminths	Eukaryotic	Multicellular; parasitic roundworms and flatworms
Viruses	Not cells; nonliving	Infect animal, plant, or bacterial cells; can have a DNA or RNA genome
Prions	Not cells; nonliving	Infectious proteins; cause transmissible spongiform encephalopathies

Virology: The Study of Viruses

Definition and Discovery

Virology is the study of viruses, which are submicroscopic, infectious agents. Viruses were discovered when infectious sap from tobacco plants remained active even after filtering out cells, indicating the presence of a non-cellular infectious entity.

Virus is Latin for "venomous secretion".
Over 5,000 mammal-infecting viral species have been described; about 220 infect humans.
Estimated over 320,000 mammalian viruses remain uncharacterized.
Approximately 70% of human-infecting viruses are harbored in other animals.

Characteristics of Viruses

Extremely small (20–400 nm).
Acellular: Not composed of cells; considered nonliving.
Obligate intracellular pathogens: Require host cells for replication; lack metabolic machinery.
Can infect all branches of the tree of life (animals, plants, bacteria).

Virus Structural Features

Virion Structure

A virion is a single, infectious virus particle. It consists of:

Capsid: Protective protein shell.
Genetic material: DNA or RNA.
Some have an outer lipid envelope.
Spikes (peplomers): Glycoprotein extensions for host cell attachment.

Capsid Structure and Function

Capsid is made of capsomere subunits (single or multiple protein types).
Self-assembly: Capsomere arrangement is determined by genome sequence.
Capsid formation is a key target for antiviral drugs.

Capsid Arrangements

Helical capsids: Hollow tube-like structure.
Icosahedral capsids: 3D polygonal structure.
Complex capsids: Deviations from helical or icosahedral, e.g., brick-shaped (poxviruses), bacteriophage structures.

Viral Envelopes and Naked Viruses

Enveloped viruses acquire a lipid membrane from the host during budding (e.g., coronaviruses, influenza, herpesviruses).
Naked viruses lack an envelope and are released by host cell lysis (e.g., human papillomavirus, poliovirus, rotavirus).
Bacteriophages are almost always naked.

Viral Spikes (Peplomers)

Spikes are glycoprotein extensions aiding in host cell attachment and entry.
Determine host range and tissue tropism.
Example: SARS-CoV-2 spike protein is a vaccine target.

Viral Genomic Features

Genome Organization

Most viruses have fewer than 100 genes.
Genomes can be DNA or RNA, single or double stranded, segmented or non-segmented, circular or linear.
Encode capsomere proteins, replication enzymes, and structural factors.

Types of Viral Genomes

dsDNA viruses: Double-stranded DNA; use host polymerases for transcription (e.g., herpesviruses, hepatitis B).
ssDNA viruses: Single-stranded DNA; converted to dsDNA before transcription (e.g., parvovirus B19).
ssRNA (+) sense: Genome acts as mRNA, directly translated (e.g., SARS-CoV-2, polio).
ssRNA (–) sense: Genome is complementary to mRNA; must be transcribed to mRNA by viral RNA-dependent RNA polymerase.
dsRNA viruses: Double-stranded RNA; require RNA-dependent RNA polymerase (e.g., rotavirus).
Retroviruses: ssRNA genome is reverse transcribed into DNA by reverse transcriptase (e.g., HIV).

Mutation and Genetic Change

Viruses mutate rapidly due to quick replication and lack of proofreading in RNA polymerases.
Mutations can be neutral, beneficial, or deleterious.
Attenuated strains (less infectious) are used in vaccines.
Beneficial mutations may increase infectivity, expand host range, or help evade immune detection.

Reassortment and Antigenic Variation

Reassortment: Occurs when two viral strains coinfect a host cell, leading to new genetic combinations.
Antigenic drift: Minor changes in viral antigens (e.g., influenza HA and NA spikes) due to mutation.
Antigenic shift: Major genetic reassortment, often leading to pandemics (e.g., COVID-19 emergence from bats to humans).

Classifying and Naming Viruses

Classification Criteria

Type of nucleic acid (DNA or RNA).
Capsid symmetry (helical, icosahedral, complex).
Presence or absence of envelope.
Genome architecture (ssDNA, dsRNA, etc.).

Host Range and Tropism

Host range: Species a virus can infect (e.g., measles infects only humans; avian flu infects birds and humans).
Tropism: Tissue or cell specificity (e.g., hepatitis viruses infect liver cells; ebola infects multiple tissue types).

Virus Naming and Taxonomy

Viruses are not assigned to domains, kingdoms, phyla, or classes.
Highest taxon is order, followed by family, genus, and species.

Viral Replication

Bacteriophage Replication

Lytic Cycle

Attachment (adsorption): Phage binds to bacterial cell.
Penetration (entry): Phage injects genetic material.
Replication (synthesis): Host cell transcribes and translates viral genes.
Assembly (maturation): New phages are assembled.
Release: Host cell lyses, releasing new phages.

Lysogenic Cycle

Phage genome integrates into host genome as a prophage.
Prophage is replicated with host cell division.
Upon stress, prophage may excise and enter lytic cycle.

Medical Importance

Phage conversion: Phages can confer new pathogenic properties to bacteria (e.g., toxin production in Corynebacterium diphtheriae, Clostridium botulinum).

Animal Virus Replication

Attachment: Virus binds to host cell via capsid proteins or spikes.
Penetration (entry): Enveloped viruses enter by endocytosis or membrane fusion; naked viruses by endocytosis.
Uncoating: Capsid is removed, releasing genome.
Replication (synthesis): Genome is replicated and viral proteins are synthesized.
Assembly: New virions are formed.
Release: Enveloped viruses bud off; naked viruses lyse the host cell.

Persistent Infections and Oncogenic Viruses

Acute infections: Rapid production of virions (e.g., common cold, flu).
Persistent infections: Virus remains in host, evading immune clearance (e.g., HIV, papillomaviruses, herpesviruses).
Oncogenic viruses: Cause cancer by stimulating uncontrolled cell division or inhibiting cell death (e.g., HPV, HTLV).

Clinical Aspects of Viruses

Laboratory Cultivation

Bacteriophages: Grown on bacterial cultures; detected by plaque assays (clear zones indicate lysis).
Animal viruses: Cultivated in tissue culture, animal hosts, or embryonated eggs.

Virus Detection Methods

Viruses are detected by molecular methods, as they are not visible by light microscopy.
Detection targets: Viral genetic material, proteins, or patient antibodies.
Specificity: Detects only the virus of interest (no false positives).
Sensitivity: Detects low levels of virus (no false negatives).

Detecting Viral Proteins

Agglutination tests: Antibodies or antigens linked to latex beads; clumping indicates presence of virus or antibodies.
ELISAs (Enzyme-Linked Immunosorbent Assays): Detect antigens or antibodies; color change indicates binding.

Limitations

Sample must be liquid.
Antigens must be well characterized.
Antigenic shift may render tests ineffective.
Antibody detection is less effective in early infection.

Detecting Viral Genetic Material

Reverse transcription PCR (rt-PCR): Detects viral RNA (e.g., SARS-CoV-2).
Sequencing: Identifies specific viral genetic segments.

Antiviral Drugs

Mechanisms and Challenges

Antivirals target steps in viral replication but usually do not cure infections.
Viruses are obligate intracellular pathogens; drugs must be selectively toxic.
Fewer distinct targets compared to living pathogens.

Types of Antiviral Drugs

Nucleoside analogs: Mimic nucleotides, block replication (e.g., acyclovir).
Nucleoside reverse transcriptase inhibitors (NRTIs): Target reverse transcriptase (e.g., AZT for HIV).
Antisense antivirals: Short nucleotide sequences bind viral RNA, inhibiting translation (e.g., Vitravene).
Interferons: Natural proteins that signal viral infection, induce defensive changes in neighboring cells; can be administered therapeutically.

Prions

Definition and Pathogenicity

Prions are infectious proteins without genetic material.
Do not replicate; misfolded prions cause destruction of brain tissue.
Cause transmissible spongiform encephalopathies (TSEs).

Types of Spongiform Encephalopathies

Inherited: Gerstmann-Straussler-Schienker syndrome, Fatal familial insomnia.
Inherited or acquired: Creutzfeldt-Jakob disease (CJD), "mad cow disease".

Key Laboratory Methods in Microbiology

Summary Table: Laboratory Methods

Method	Purpose	Example/Application
Agglutination Tests	Detect viral antigens or antibodies	Latex bead clumping
ELISAs	Detect antigens or antibodies	Color change on surface
PCR/rt-PCR	Detect viral genetic material	SARS-CoV-2 detection
Sequencing	Identify viral genetic segments	Genomic analysis

Summary

Viruses and prions are nonliving agents studied in microbiology.
Viruses have diverse structures, genomes, and replication strategies.
Classification is based on nucleic acid type, capsid symmetry, envelope presence, and genome architecture.
Laboratory methods include agglutination tests, ELISAs, PCR, and sequencing.
Antiviral drugs target replication steps; prions cause neurodegenerative diseases.

Additional info: Some explanations and examples were expanded for clarity and completeness based on standard microbiology curriculum.