Viruses, Viroids, and Prions

General Characteristics of Viruses

Viruses are unique infectious agents that differ fundamentally from bacteria and other microorganisms. They are obligatory intracellular parasites, meaning they require living host cells to multiply. Viruses contain either DNA or RNA as their genetic material, but never both, and are surrounded by a protein coat called a capsid. Unlike bacteria, viruses lack ribosomes and an ATP-generating mechanism, relying entirely on the host cell's machinery for replication.

• Obligatory intracellular parasites: Must invade living cells to reproduce.

• Genetic material: DNA or RNA, single- or double-stranded, linear, circular, or segmented.

• Protein coat: Capsid made of capsomeres.

• No ribosomes or ATP generation: Cannot synthesize proteins or generate energy independently.

Comparison of Viruses and Bacteria

Viruses and bacteria differ in several key aspects, as summarized in the following table:

Virus Sizes

Viruses are much smaller than most bacteria and eukaryotic cells, with sizes ranging from 20 nm (prions) to nearly 1000 nm (Ebola virus). The following image illustrates the relative sizes and shapes of various viruses and cells:

Host Range

The host range of a virus refers to the spectrum of host cells it can infect. Most viruses are highly specific, infecting only certain cell types within a single host species. This specificity is determined by the presence of specific attachment sites on the host cell and compatible cellular factors.

• Bacteriophages: Infect bacteria; receptor sites may be on cell wall, fimbriae, or flagella.

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

Influenza: Antigenic Shift

Influenza viruses can undergo antigenic shift when genes from human and animal flu viruses mix in a pig, potentially creating a new virus capable of infecting humans and causing pandemics.

Viral Structure

The virion is the complete, fully developed viral particle. Its structure includes:

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

• Capsid: Protein coat made of capsomeres.

• Envelope: Lipid, protein, and carbohydrate coating present in some viruses, often derived from the host cell membrane.

• Spikes: Projections from the envelope, used for attachment.

Capsid and Envelope

The capsid is composed of protein subunits called capsomeres. The envelope, present in some viruses, is external to the capsid and may contain spikes for attachment.

General Morphology of Viruses

Viruses exhibit several morphological types:

• Helical viruses: Hollow, cylindrical capsid (e.g., rabies, Ebola).

• Polyhedral viruses: Many-sided, often icosahedral (e.g., adenovirus, poliovirus).

• Enveloped viruses: Spherical or irregular shapes.

• Complex viruses: Complicated structures (e.g., bacteriophage).

Polyhedral Virus Morphology

Enveloped Helical Virus Morphology

Helical Virus Morphology

Complex Virus Morphology

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 various compartments; growth indicated by changes or death of embryo. Used for vaccine production.

• In cell cultures: Primary cell lines, diploid cell lines (from human embryos), and continuous cell lines (from cancerous cells, e.g., HeLa).

Viral Identification

Viruses are identified by:

• Cytopathic effects: Visible changes in cell cultures.

• Serological tests: Rapid antigen tests, ELISA (antibody-based detection).

• Nucleic acid tests: PCR (polymerase chain reaction).

Viral Multiplication

Viruses multiply by invading host cells and taking over their metabolic machinery. A single virion can produce thousands of progeny in one cell. The one-step growth curve illustrates the phases of viral replication.

Multiplication of Bacteriophages

Bacteriophages multiply via two mechanisms:

• Lytic cycle: Phage causes lysis and death of the host cell (e.g., Tequatrovirus).

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

The Lytic Cycle of T-Even Bacteriophage

• Attachment: Phage attaches to host cell via tail fibers.

• Penetration: Phage injects DNA into host cell.

• Biosynthesis: Host cell synthesizes viral components.

• Maturation: Assembly of new virions.

• Release: Host cell lyses, releasing new phages.

The Lysogenic Cycle of Lambdavirus Bacteriophage

• Lysogeny: Phage DNA integrates into host chromosome as a prophage.

• Replication: Host cell replicates, passing prophage DNA to daughter cells.

• Phage conversion: Host cell acquires new properties (e.g., toxin production).

• Specialized transduction: Specific bacterial genes transferred via phage.

Comparison of Bacteriophage and Animal Virus Multiplication

Multiplication of Animal Viruses

• Attachment: Viruses attach to cell membrane.

• Entry: By receptor-mediated endocytosis or fusion.

• Uncoating: Viral nucleic acid separated from capsid.

• Biosynthesis: Production of nucleic acid and proteins.

• Maturation: Assembly of nucleic acid and capsid proteins.

• Release: By budding (enveloped viruses) or rupture (nonenveloped viruses).

Biosynthesis of DNA and RNA Viruses

DNA Viruses

DNA viruses replicate their DNA in the nucleus using host enzymes and synthesize capsid proteins in the cytoplasm. Assembly occurs in the nucleus.

RNA Viruses

RNA viruses multiply in the cytoplasm using RNA-dependent RNA polymerase. The replication pathway depends on whether the viral RNA is sense (+), antisense (−), or double-stranded.

Retroviruses

Retroviruses use reverse transcriptase to produce DNA from their RNA genome, which integrates into the host chromosome as a provirus.

Viruses and Cancer

Some viruses can cause cancer by transforming normal cells into tumor cells. Proto-oncogenes are normal genes that, when mutated, become oncogenes and can induce cancer. Oncogenic viruses integrate into host DNA and induce transformation.

• Sarcoma: Cancer of connective tissue.

• Adenocarcinoma: Cancer of glandular epithelial tissue.

• Oncolytic viruses: Used to treat cancer by infecting and killing tumor cells.

Latent and Persistent Viral Infections

Latent viral infections remain dormant in host cells and may reactivate. Persistent infections progress slowly and are often fatal.

• Latent: Herpesviruses (cold sores, shingles).

• Persistent: HIV/AIDS, hepatitis B, subacute sclerosing panencephalitis.

Prions

Prions are infectious proteins, not viruses. They cause diseases such as mad cow disease and Creutzfeldt-Jakob disease by converting normal cellular prion protein (PrPC) into a misfolded, infectious form (PrPSC).

• Inherited and transmissible: By ingestion, transplant, or surgical instruments.

• Spongiform encephalopathies: Characterized by brain plaques and cell death.

Summary Table: Latent and Persistent Viral Infections

Key Terms and Concepts

• Virion: Complete viral particle.

• Capsid: Protein coat surrounding nucleic acid.

• Envelope: Lipid, protein, and carbohydrate layer external to capsid.

• Prophage: Phage DNA integrated into bacterial chromosome.

• Oncogene: Gene that can transform a cell into a cancer cell.

• Prion: Infectious protein causing neurodegenerative disease.