Viruses, Viroids, and Prions: Structure, Replication, and Pathogenesis

Viruses, Viroids, and Prions

Introduction to Viruses

Viruses are acellular infectious agents that require living host cells for replication. They are much smaller than bacteria and possess unique structural and genetic features that distinguish them from other microorganisms.

• Obligate intracellular parasites: Viruses cannot replicate outside a host cell; they depend on host cellular machinery for reproduction.

• Relative size: Viruses typically range from 20 to 300 nanometers, much smaller than most bacteria.

Basic Structural Makeup of Viruses

• Naked viruses: Consist of a nucleic acid genome surrounded by a protein coat called a capsid. They lack an outer lipid envelope.

• Enveloped viruses: Possess a nucleocapsid (genome + capsid) surrounded by a lipid envelope derived from the host cell membrane. The envelope contains viral glycoproteins (spikes).

• Key structures:

  • Nucleic acid: DNA or RNA (never both), single- or double-stranded.

  • Capsid: Protein shell composed of subunits called capsomeres.

  • Envelope: Lipid bilayer with embedded viral proteins (in enveloped viruses).

  • Spikes/Glycoproteins: Surface proteins involved in host cell recognition and attachment.

  • Tail fibers: Found in some bacteriophages, used for attachment to bacterial cells.

Viral Genome Arrangements

Viral genomes are highly diverse in structure and composition.

• Types of nucleic acids: DNA or RNA.

• Strandedness: Single-stranded (ss) or double-stranded (ds).

• Sense: For ssRNA viruses, genomes can be positive-sense (+) or negative-sense (−).

• Shape: Linear, circular, or segmented genomes.

Function of Tail Fibers and Glycoproteins

• Attachment: Tail fibers (in bacteriophages) and glycoprotein spikes (in animal viruses) mediate specific binding to host cell receptors.

• Host specificity: The interaction between viral proteins and host receptors determines the host range and tissue tropism of the virus.

Basic Shapes of Viral Particles

• Icosahedral: Spherical appearance, 20-sided structure (e.g., Adenovirus).

• Helical: Rod-shaped, with nucleic acid coiled inside a helical capsid (e.g., Tobacco mosaic virus).

• Complex: Structures not purely icosahedral or helical, often with additional components (e.g., bacteriophage T4 with head, tail, and tail fibers).

Lytic Phage and the Lytic Cycle

Lytic phages are bacteriophages that replicate within and lyse their bacterial host cells.

1. Attachment: Phage binds to specific receptors on the bacterial surface.

2. Penetration: Phage injects its genome into the host cell.

3. Synthesis: Host machinery synthesizes viral components (nucleic acids and proteins).

4. Assembly: New phage particles are assembled from synthesized components.

5. Release: Host cell lyses, releasing new phage particles.

Temperate Phage and the Lysogenic Cycle

Temperate phages can undergo both lytic and lysogenic cycles. In the lysogenic cycle, the phage genome integrates into the host chromosome as a prophage and replicates along with the host cell without causing lysis.

• Lysogenic cycle: Phage DNA integrates into host genome and is passively replicated.

• Induction: Environmental triggers can cause the prophage to excise and enter the lytic cycle.

• Relationship to lytic cycle: Lysogeny allows phage persistence without killing the host; lytic cycle results in host cell death.

Transduction: Generalized vs. Specialized

Transduction is the process by which bacterial DNA is transferred from one bacterium to another by a virus (bacteriophage).

Type	Mechanism	DNA Transferred
Generalized Transduction	Random bacterial DNA is packaged into phage during lytic cycle	Any gene from donor bacterium
Specialized Transduction	Specific bacterial genes near prophage site are transferred during excision of lysogenic phage	Only genes adjacent to prophage integration site

Horizontal gene transfer: Both mechanisms allow for the movement of bacterial genes between cells, contributing to genetic diversity.

Animal Virus Replication Cycle

Animal viruses follow a general replication cycle with some differences from bacteriophages, especially in entry and exit mechanisms.

1. Attachment: Viral glycoproteins bind to specific receptors on the animal cell membrane, determining host specificity.

2. Entry: Two main mechanisms:

   • Membrane fusion: Enveloped viruses fuse with the host membrane, releasing the nucleocapsid into the cytoplasm.

   • Endocytosis: Virus is engulfed by the cell and enters via vesicles; uncoating releases the genome.

3. Uncoating: Viral capsid is removed, exposing the genome.

4. Synthesis: Viral genome is replicated and viral proteins are synthesized. The process depends on the type of viral genome (DNA, RNA, positive-sense, negative-sense).

5. Assembly: New virions are assembled from synthesized components.

6. Release: Two main mechanisms:

   • Budding: Enveloped viruses acquire their envelope from the host cell membrane as they exit.

   • Cell lysis: Non-enveloped viruses are released by host cell rupture.

• Central dogma: Normal flow of genetic information is DNA → RNA → Protein. Some viruses (e.g., retroviruses) reverse this flow using reverse transcriptase.

Cultivation and Quantitation of Viruses

• Cell cultures: Viruses are grown in living cells (animal, plant, or bacterial cultures).

• Cytopathic effects (CPE): Observable changes in host cells due to viral infection (e.g., cell rounding, detachment, lysis).

• Viral growth curve: Describes the phases of viral replication (eclipse, maturation, release).

• Plaque assay: Quantifies infectious virus particles by counting clear zones (plaques) formed on a cell monolayer.

• Direct counts: Physical counting of virus particles using electron microscopy or other methods.

Viroids

Viroids are small, circular, single-stranded RNA molecules that infect plants. They lack a protein coat and do not encode proteins, yet can cause significant plant diseases by interfering with host gene expression.

Prions and Transmissible Spongiform Encephalopathies (TSEs)

• Prions: Infectious proteins that lack nucleic acids. They cause disease by inducing abnormal folding of normal host proteins.

• Transmissible spongiform encephalopathies (TSEs): A group of fatal neurodegenerative diseases caused by prions (e.g., Creutzfeldt-Jakob disease, mad cow disease).

• Propagation mechanism: Prions convert normal cellular prion protein (PrPC) into the misfolded, disease-causing form (PrPSc), which accumulates in neural tissue.