Viruses and Prions

Distinctive Features of Viruses

Viruses are unique infectious agents characterized by their dependence on living host cells for replication. They possess distinct structural and functional properties that differentiate them from other microorganisms.

• Obligatory intracellular parasites: Viruses require living host cells to multiply, as they lack the necessary cellular machinery for independent replication.

• Genetic material: Viruses contain either DNA or RNA, but never both.

• Protein coat: The viral genome is enclosed within a protein coat called the capsid.

• No ribosomes or ATP-generating mechanism: Viruses rely entirely on the host cell for protein synthesis and energy production.

Virus Sizes

Viruses vary greatly in size, typically ranging from 20 nm to 900 nm, which is much smaller than most bacteria and eukaryotic cells.

• Examples include poliovirus (30 nm), rabies virus (170 x 70 nm), and Ebola virus (970 nm).

Host Range

The host range of a virus refers to the spectrum of host cells it can infect.

• Most viruses infect only specific types of cells in one host, determined by specific attachment sites and cellular factors.

• Bacteriophages: Viruses that infect bacteria; receptor sites may be part of the cell wall, fimbriae, or flagella.

• Animal viruses: Receptor sites are typically on the plasma membrane.

Viral Structure

Virion Structure

The virion is the complete, fully developed viral particle. Its structure includes nucleic acid, capsid, envelope (in some viruses), and spikes.

• Nucleic acid: DNA or RNA, single- or double-stranded, linear, circular, or segmented.

• Capsid: Protein coat made of subunits called capsomeres.

• Envelope: Lipid, protein, and carbohydrate coating present in some viruses.

• Spikes: Projections from the outer surface, often used for attachment.

Capsid and Envelope

• Capsid: Composed of capsomeres; protects the viral genome.

• Envelope: Present in some viruses, derived from the host cell membrane during budding; contains viral proteins and spikes.

• Spikes: Glycoprotein projections used for attachment to host cells.

General Morphology

Viruses are classified based on their morphology:

• Helical viruses: Hollow, cylindrical capsid; e.g., rabies and Ebola viruses.

• Polyhedral viruses: Many-sided, most commonly icosahedral; e.g., adenoviruses and poliovirus.

• Enveloped viruses: Spherical with a lipid envelope.

• Complex viruses: Complicated structures, such as bacteriophages.

Taxonomy of Viruses

Baltimore Classification System

The Baltimore classification system categorizes viruses based on their nucleic acid type and the method of mRNA production.

• Seven groups referred to as "realms".

• Genus names end in -virus, family names in -viridae, and order names in -ales.

• Viral species: Group of viruses sharing genetic information and ecological niche.

Isolation, Cultivation, and Identification of Viruses

Growing Bacteriophages

• Bacteriophages are grown in bacteria, forming plaques (clearings) on a lawn of bacteria.

• Each plaque corresponds to a single virus and can be quantified as plaque-forming units (PFU).

Growing Animal Viruses

• In living animals: Mice, rabbits, guinea pigs.

• In embryonated eggs: Virus injected into the egg; growth signaled by changes or death of the embryo. Used for vaccine production.

• In cell cultures: Primary cell lines are preferred; cells form a monolayer and cytopathic effects (CPE) indicate viral infection.

• Continuous cell lines: Derived from cancerous cells, can be maintained indefinitely (e.g., HeLa cell line).

Viral Multiplication

One-Step Growth Curve

Viral multiplication involves invasion of a host cell and takeover of its metabolic machinery. A single virion can produce thousands of progeny.

• The one-step growth curve illustrates the eclipse period and release of virions.

Multiplication of Bacteriophages

Bacteriophages multiply via two mechanisms:

• Lytic cycle: Phage causes lysis and death of the host cell.

• Lysogenic cycle: Phage DNA is incorporated into the host DNA, remaining latent as a prophage.

Lytic Cycle Steps

1. Attachment: Phage attaches to host cell.

2. Penetration: Phage injects DNA into host.

3. Biosynthesis: Production of phage DNA and proteins.

4. Maturation: Assembly of phage particles.

5. Release: Host cell lyses, releasing new phages.

Lysogenic Cycle Steps

• Phage DNA integrates into host DNA as a prophage.

• Prophage is replicated with host chromosome.

• Induction can trigger entry into the lytic cycle.

Outcomes of Lysogeny

1. Lysogenic host cells are immune to reinfection by the same phage.

2. Phage conversion: Host cell exhibits new properties encoded by prophage DNA (e.g., diphtheria toxin production).

3. Specialized transduction: Specific bacterial genes transferred to another bacterium via a phage.

Multiplication of Animal Viruses

Animal viruses multiply through a series of steps:

1. Attachment: Viruses attach to cell membrane.

2. Entry: By receptor-mediated endocytosis or fusion.

3. Uncoating: Viral nucleic acid separated from capsid.

4. Biosynthesis: Production of nucleic acid and proteins.

5. Maturation: Assembly of viral components.

6. Release: By budding (enveloped viruses) or rupture (naked viruses).

Biosynthesis of DNA Viruses

DNA viruses replicate their DNA in the nucleus and synthesize capsid proteins in the cytoplasm.

• Example: Adenoviridae (double-stranded DNA, naked) causes respiratory infections.

• Steps: Attachment, penetration, uncoating, early transcription/translation, DNA replication, late transcription/translation, maturation, release.

Biosynthesis of RNA Viruses That Use DNA

Some RNA viruses, such as Retroviridae, use reverse transcriptase to produce DNA from their RNA genome.

• Viral DNA integrates into the host chromosome as a provirus.

• Example: Lentivirus (HIV), Oncoviruses.

Bacteriophage and Animal Viral Multiplication Compared

Viruses and Cancer

Oncogenic Viruses

Certain viruses can cause cancer by integrating their genetic material into the host cell's DNA, leading to transformation.

• Proto-oncogenes: Genes involved in stimulating normal cell growth; mutations convert them to oncogenes.

• Oncogenes: Transform normal cells into cancerous cells.

• Transformed cells lack apoptosis, have increased growth, and express tumor-specific transplantation antigens (TSTA).

• Examples: Epstein-Barr virus (Burkitt’s lymphoma), Human papillomavirus (HPV; cervical and anal cancer), Hepatitis B virus.

Latent and Persistent Viral Infections

Latent Viral Infections

• Virus remains in asymptomatic host cell for long periods.

• All herpesviruses are capable of latency; may reactivate due to changes in immunity.

• Examples: HHV1 (cold sores), Varicellovirus (shingles).

Persistent Viral Infections

• Occurs gradually over a long period; generally fatal.

• Example: HIV/AIDS.

Prions

Structure and Pathogenicity

Prions are infectious proteins that cause neurodegenerative diseases.

• PrPc: Normal cellular prion protein found on cell surfaces.

• PrPSc: Misfolded, infectious form that accumulates in brain cells, forming plaques.

• Disease results from conversion of PrPc to PrPSc.

• Transmissible by ingestion, transplant, and surgical instruments.

• Diseases: Mad cow disease, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, sheep scrapie.

Summary Table: Key Differences Between Viruses and Prions

Additional info: Academic context was added to clarify viral replication steps, prion pathogenicity, and the Baltimore classification system.