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

Chapter 13: Viruses, Viroids, and Prions

Distinctive Features of Viruses

Viruses are unique infectious agents with several distinctive features that set them apart from other microorganisms.

• Obligatory intracellular parasites: Viruses require living host cells to multiply, as they cannot reproduce independently.

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

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

• Host cell machinery: Viruses multiply by using the host cell’s synthesizing machinery.

• Lack of cellular components: Viruses do not possess ribosomes or an ATP-generating mechanism.

Comparison of Viruses and Bacteria

Viruses differ from bacteria in several fundamental ways, as summarized in the following table:

Feature	Bacteria	Rickettsias/Chlamydias	Viruses
Intracellular Parasite	No	Yes	Yes
Plasma Membrane	Yes	Yes	No
Binary Fission	Yes	Yes	No
Pass through Filters	No	No/Yes	Yes
DNA and RNA	Yes	Yes	No
ATP Metabolism	Yes	Yes/No	No
Ribosomes	Yes	Yes	No
Sensitive to Antibiotics	Yes	Yes	No
Sensitive to Interferon	No	No	Yes

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 host 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.

Virus Sizes

Viruses vary greatly in size, from 20 nm (prions) to nearly 1 µm (Ebola virus). Their size is much smaller than most bacteria and human cells.

Viral Structure

The complete, fully developed viral particle is called a virion. Virions consist of:

• 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, 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 spikes for attachment.

General Morphology of Viruses

Viruses are classified by their morphology:

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

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

• Enveloped viruses: Spherical, with an envelope.

• Complex viruses: Complicated structures; e.g., bacteriophages.

Taxonomy of Viruses

The Baltimore classification system categorizes viruses based on their nucleic acid and how their mRNA is produced. Viral taxonomy uses:

• Genus: Ends in -virus

• Family: Ends in -viridae

• Order: Ends in -ales

• Viral species: Group sharing genetic information and ecological niche

Growing Viruses in the Laboratory

Bacteriophages

Bacteriophages are grown in bacteria and form plaques (clearings) on a lawn of bacteria on agar. Each plaque corresponds to a single virus and can be quantified as plaque-forming units (PFU).

Animal Viruses

• In living animals: Mice, rabbits, guinea pigs; not all human viruses grow or cause disease in animals.

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

• In cell cultures: Cells separated by enzymes, suspended in nutrient solution, and grown as a monolayer. Viruses cause visible changes (cytopathic effect, CPE).

• Primary cell lines: Die out after a few generations.

• Diploid cell lines: Derived from human embryos, maintained for about 100 generations.

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

Viral Identification

• Cytopathic effects: Observed in cell culture.

• Serological tests: ELISA detects virus by antibody reaction.

• Nucleic acid tests: PCR amplifies viral genetic material.

Viral Multiplication

Viruses multiply by invading a host cell and taking over its metabolic machinery. A single virion can produce thousands of progeny in a host cell. The one-step growth curve illustrates the process:

Multiplication of Bacteriophages

Lytic Cycle

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

• Penetration: Phage lysozyme opens cell wall; DNA injected.

• Biosynthesis: Production of phage DNA and proteins; host protein synthesis halted.

• Maturation: Assembly of phage particles.

• Release: Phage lysozyme breaks cell wall, releasing new phages.

Lysogenic Cycle

• Lysogeny: Phage DNA incorporates into host DNA as a prophage; host cell is not lysed.

• Replication: Host cell replicates prophage DNA.

• 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.

Comparison of Bacteriophage and Animal Viral Multiplication

The following table summarizes the differences between 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 by enzymes.

• 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 Viruses

• DNA viruses replicate their DNA in the nucleus using host enzymes.

• Capsid proteins are synthesized in the cytoplasm and migrate to the nucleus for assembly.

Biosynthesis of RNA Viruses

• RNA viruses multiply in the cytoplasm using RNA-dependent RNA polymerase.

• ssRNA (+ strand): Viral RNA serves as mRNA for protein synthesis.

• ssRNA (− strand): Viral RNA is transcribed to a + strand to serve as mRNA.

• dsRNA: Double-stranded RNA viruses.

Biosynthesis of RNA Viruses That Use DNA

• Single-stranded RNA viruses produce DNA using reverse transcriptase.

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

• Retroviridae: Includes Lentivirus (HIV) and Oncoviruses.

Viruses and Cancer

• Some cancers are caused by viruses, which may develop long after infection.

• Sarcoma: Cancer of connective tissue.

• Adenocarcinomas: Cancers of glandular epithelial tissue.

Transformation of Normal Cells Into Tumor Cells

• Proto-oncogenes: Genes encoding proteins for normal cell growth.

• Oncogenes: Mutated proto-oncogenes that transform cells into cancerous cells.

• Oncogenic viruses: Integrated into host DNA, induce tumors.

• Tumor-specific transplantation antigen (TSTA): Found on surface of transformed cells.

DNA Oncogenic Viruses

• Adenoviridae

• Herpesviridae: Epstein-Barr virus (Burkitt’s lymphoma)

• Poxviridae

• Papovaviridae: Human papillomavirus (HPV; cervical and anal cancer)

• Hepadnaviridae: Hepatitis B virus

RNA Oncogenic Viruses

• Retroviridae: HTLV-1 and HTLV-2 (adult T cell leukemia and lymphoma), FeLV (feline leukemia virus)

Viruses to Treat Cancer

• Oncolytic viruses: Infect and kill tumor cells or stimulate immune response against tumors.

Latent and Persistent Viral Infections

• Latent infections: Virus remains in host cell without symptoms; may reactivate (e.g., herpesviruses, cold sores, shingles).

• Persistent infections: Virus is continuously released, causing gradual disease progression (e.g., HIV/AIDS, liver cancer).

Disease	Primary Effect	Causative Virus
Cold sores	Skin and mucous membrane lesions; genital lesions	HHV-1 and HHV-2
Leukemia	Increased white blood cell growth	HTLV-1 and -2
Shingles	Skin lesions	Varicellovirus (Herpesvirus)
Cervical cancer	Increased cell growth	Human papillomavirus
HIV/AIDS	Decreased CD4+ T cells	HIV-1 and -2 (Lentivirus)
Liver cancer	Increased cell growth	Hepatitis B virus
Persistent enterovirus infection	Mental deterioration associated with AIDS	Echoviruses
Progressive encephalitis	Rapid mental deterioration	Rubella virus
Subacute sclerosing panencephalitis (SSPE)	Mental deterioration	Measles virus

Plant Viruses and Viroids

• Plant viruses: Enter through wounds or via insects; cause diseases in economically valuable plants.

• Viroids: Short pieces of naked RNA; cause diseases such as potato spindle tuber disease.

• Virusoids: Viroids enclosed in a protein coat; cause disease only when coinfected with a virus.

Prions

Prions are proteinaceous infectious particles, inherited and transmissible by ingestion, transplant, and surgical instruments.

• Spongiform encephalopathies: Includes "mad cow disease," Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and sheep scrapie.

• Normal cellular prion protein (cPrP): Found on cell surface.

• Scrapie protein (ScPrP): Accumulates in brain cells, forming plaques.

• Disease is caused by conversion of cPrP into ScPrP, a misfolded infectious form.