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Characterizing and Classifying Viruses, Viroids, and Prions

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Characterizing and Classifying Viruses, Viroids, and Prions

Characteristics of Viruses

Viruses are acellular, infectious agents that lack the structures and metabolic machinery of living cells. They are obligate intracellular parasites, meaning they require a host cell to reproduce and carry out metabolic processes.

  • Definition: A virus is a minuscule, acellular agent composed of nucleic acid (DNA or RNA) surrounded by a protein coat (capsid). Some viruses also possess a phospholipid envelope.

  • Virion: The extracellular state of a virus, consisting of the nucleic acid and capsid (nucleocapsid), and sometimes an envelope.

  • Intracellular State: Once inside a host cell, the capsid is removed, and the virus exists as nucleic acid.

  • Key Features:

    • No cytoplasmic membrane, organelles, or cytosol.

    • Cannot metabolize, grow, or respond to the environment independently.

  • Example: Tobacco Mosaic Virus (TMV) was the first virus to be isolated and visualized using electron microscopy.

Genetic Material of Viruses

Viral genomes are highly variable and are a key basis for classification.

  • Types of Nucleic Acid: DNA or RNA, which may be single-stranded (ss) or double-stranded (ds).

  • Genome Forms: Linear or circular, single or multiple molecules.

  • Genome Size: Much smaller than cellular genomes (e.g., bacteriophage MS2 has only 3 genes).

  • Classification: Based on nucleic acid type: dsDNA, ssDNA, dsRNA, or ssRNA.

Hosts of Viruses

Viruses infect a wide range of hosts, but most are specific to certain cell types due to molecular recognition.

  • Host Range: Archaea, bacteria, plants, protozoa, fungi, and animals.

  • Specificity: Determined by affinity between viral surface proteins/glycoproteins and host cell receptors.

  • Bacteriophage (Phage): Viruses that infect bacteria.

  • Fungal Viruses: Often lack an extracellular stage; spread by cell fusion.

Sizes of Viruses

Viruses are among the smallest infectious agents.

  • Size Range: 17 nm (smallest) to 500 nm (largest).

  • Visualization: Most cannot be seen with light microscopy; electron microscopy is required.

Capsid Morphology

The capsid is the protein shell that encases the viral genome.

  • Capsomeres: Protein subunits that make up the capsid; may be identical or diverse.

  • Functions: Protects the genome and aids in host cell attachment.

Viral Shapes

Viruses are classified by their shape, which is determined by the arrangement of capsomeres.

  • Helical: Capsomeres form a tube around the nucleic acid (e.g., TMV).

  • Polyhedral: Roughly spherical, often icosahedral (20 faces).

  • Complex: Irregular shapes, often with additional structures (e.g., bacteriophage T4).

The Viral Envelope

Some viruses possess an envelope derived from the host cell membrane.

  • Envelope: Phospholipid bilayer with embedded viral proteins (matrix proteins).

  • Enveloped Virion: Virus with an envelope; more fragile but less easily recognized by the immune system.

  • Naked Virion: Virus lacking an envelope; more stable but more immunogenic.

  • Acquisition: Envelope is acquired during viral replication or release from the host cell.

Classification of Viruses

Viruses are classified based on several criteria.

  • Criteria: Type of nucleic acid, presence of envelope, shape, and size.

  • Naming: Family and genus names are used; species are designated by common English names in italics (e.g., rabies virus).

Viral Replication

Lytic Replication of Bacteriophages

The lytic cycle results in the destruction (lysis) of the host cell and release of new virions.

  1. Attachment: Virion attaches to host cell via specific interactions.

  2. Entry: Viral DNA is injected into the host; lysozyme weakens the cell wall.

  3. Synthesis: Host DNA is degraded; viral genome is replicated and proteins synthesized.

  4. Assembly: Capsomeres assemble spontaneously; genome is packaged.

  5. Release: Lysozyme causes cell lysis, releasing new virions.

Lysogenic Replication of Bacteriophages

Some phages integrate their genome into the host's DNA, remaining dormant for generations.

  • Lysogeny: Viral genome (prophage) integrates into host chromosome.

  • Temperate Phages: Phages capable of lysogeny (e.g., lambda phage).

  • Lysogenic Conversion: Prophage genes can alter host phenotype (e.g., toxin production).

  • Induction: Prophage may excise and enter the lytic cycle.

Replication of Animal Viruses

Animal viruses follow similar steps as bacteriophages but with notable differences due to host cell structure and presence of viral envelopes.

Attachment

  • Attachment is mediated by glycoprotein spikes or capsid proteins; no tail fibers.

Entry and Uncoating

  • Direct Penetration: Naked viruses create a pore for genome entry.

  • Membrane Fusion: Enveloped viruses fuse with host membrane, releasing capsid.

  • Endocytosis: Entire virion is engulfed; uncoating releases genome.

Synthesis

  • dsDNA Viruses: Replicate in nucleus; similar to host DNA replication.

  • ssDNA Viruses: Host enzymes synthesize complementary DNA; forms hairpin loops for replication.

  • +ssRNA Viruses: Genome acts as mRNA; translated directly by host ribosomes.

  • Retroviruses: +ssRNA is reverse transcribed to DNA, which integrates into host genome (e.g., HIV).

  • –ssRNA Viruses: Carry RNA-dependent RNA transcriptase to synthesize mRNA from –RNA.

  • dsRNA Viruses: +RNA strand is translated; both strands serve as templates for replication.

Assembly and Release

  • Assembly: DNA viruses assemble in the nucleus; RNA viruses in the cytoplasm.

  • Release: Enveloped viruses bud from membranes; naked viruses may cause lysis or be extruded.

  • Persistence: Budding allows prolonged infection without immediate cell death.

Latency

  • Some animal viruses (e.g., HIV, herpesviruses) can remain dormant as proviruses integrated into host DNA; may persist for years.

  • Unlike lysogeny, provirus integration is permanent; induction does not occur.

The Role of Viruses in Cancer

Viruses can contribute to the development of cancer (oncogenesis) by disrupting normal cell cycle regulation.

  • Neoplasia: Uncontrolled cell division; forms tumors (benign or malignant).

  • Metastasis: Spread of malignant cells to other tissues.

  • Viral Oncogenesis: Viruses may activate protooncogenes or inhibit tumor suppressor genes, leading to cancer.

  • Examples: Hodgkin’s disease, Kaposi’s sarcoma, cervical cancer.

Culturing Viruses in the Laboratory

Viruses require living cells for propagation, so specialized methods are used for their culture.

Culturing in Mature Organisms

  • Bacteriophages are cultured in bacterial hosts; plaques on agar plates indicate lysis.

  • Plaque assay is used to estimate phage numbers.

Culturing in Embryonated Chicken Eggs

  • Fertilized eggs provide a sterile, nutrient-rich environment for viral growth.

  • Used in vaccine production.

Culturing in Cell (Tissue) Culture

  • Diploid Cell Cultures: Derived from embryonic cells; limited lifespan.

  • Continuous Cell Cultures: Derived from tumor cells; divide indefinitely.

Are Viruses Alive?

Viruses lack many characteristics of life (growth, self-reproduction, metabolism, responsiveness), but they possess some features of living entities when inside host cells.

  • Use sophisticated mechanisms to invade and control host cells.

  • Possess genomes for replication.

  • Evolve over time.

  • Debate continues over whether viruses are truly alive.

Other Parasitic Particles: Viroids and Prions

Characteristics of Viroids

Viroids are infectious agents composed solely of a short strand of circular, single-stranded RNA without a protein coat.

  • Infect plants, causing various diseases.

  • Pathogenicity involves binding to complementary mRNA, leading to degradation by cellular enzymes.

  • Viroidlike agents infect some fungi; no known animal viroid diseases.

Characteristics of Prions

Prions are infectious proteins that cause neurodegenerative diseases by inducing abnormal folding of normal cellular proteins.

  • PrP Protein: Normal cellular PrP (c-PrP) is involved in brain function; prion PrP (p-PrP) is misfolded and pathogenic.

  • Replication: Prion PrP acts as a template, converting c-PrP into p-PrP (templating).

  • Pathology: Accumulation of p-PrP leads to neuronal death and spongiform brain appearance.

  • Diseases: Bovine spongiform encephalopathy (BSE, "mad cow disease"), scrapie (sheep), variant Creutzfeldt-Jakob disease (humans).

  • Resistance: Not destroyed by normal cooking or sterilization; destroyed by incineration or specific enzymes.

  • Prevention: Avoid feeding animal-derived proteins to livestock.

Summary Table: Key Features of Viruses, Viroids, and Prions

Agent

Genetic Material

Protein Coat

Envelope

Host Range

Replication

Diseases

Virus

DNA or RNA (ss or ds)

Present (capsid)

May be present

All life forms

Requires host cell

Many (e.g., influenza, HIV)

Viroid

ssRNA (circular)

Absent

Absent

Plants (some fungi)

Host enzymes

Plant diseases

Prion

None

Protein only

Absent

Animals (esp. mammals)

Converts normal proteins

Spongiform encephalopathies

Key Equations and Concepts

  • Viral Genome Types:

    • dsDNA, ssDNA, dsRNA, ssRNA (+ or – sense)

  • Reverse Transcription (Retroviruses):

    • Reverse transcriptase catalyzes:

  • Viral Replication Steps:

    • Attachment Entry $\rightarrow$ Synthesis $\rightarrow$ Assembly $\rightarrow$ Release

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