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

Viruses, Viroids, and Prions

Distinctive Features of Viruses

Viruses are unique infectious agents that differ significantly from cellular life forms. They are obligate intracellular parasites, meaning they require living host cells to multiply. Viruses contain either DNA or RNA (never both), which may be single- or double-stranded, and are surrounded by a protein coat called a capsid. They lack ribosomes and ATP-generating mechanisms, relying entirely on the host cell's machinery for replication.

• Obligate intracellular parasites: Cannot reproduce outside a host cell.

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

• Capsid: Protein coat made of capsomeres.

• No ribosomes or ATP production: Dependent on host cell for protein synthesis and energy.

Comparison of Viruses and Bacteria

Viruses and bacteria differ in several fundamental ways, as summarized in the table below:

Feature	Bacteria	Rickettsias/Chlamydias	Viruses
Intracellular Parasite	No	Yes	Yes
Plasma Membrane	Yes	Yes	No
Binary Fission	Yes	Yes	No
Pass through Bacteriological Filters	No	No/Yes	Yes
Possess Both DNA and RNA	Yes	Yes	No
ATP-Generating 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 are highly specific, infecting only certain cell types within a single host species. This specificity is determined by the presence of suitable attachment sites and cellular factors.

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

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

Viral Structure

Virion Components

A virion is a complete, fully developed viral particle. Its main components include:

• 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, derived from the host cell membrane.

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

General Morphology of Viruses

Viruses exhibit several morphological types:

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

• Polyhedral viruses: Many-sided, usually icosahedral (e.g., adenoviruses, poliovirus).

• Enveloped viruses: Spherical, with a lipid envelope (e.g., influenza, herpesviruses).

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

Taxonomy and Classification of Viruses

Baltimore Classification System

Viruses are classified based on their nucleic acid type and replication strategy. The Baltimore system divides viruses into seven groups (realms) based on how their mRNA is produced. Viral taxonomy uses the following conventions:

• Genus names: End in -virus

• Family names: End in -viridae

• Order names: End in -ales

• Viral species: Group of viruses sharing genetic information and ecological niche (host)

Isolation, Cultivation, and Identification of Viruses

Growing Bacteriophages

Bacteriophages are grown in bacteria. They 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).

Growing Animal Viruses

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

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

• In cell cultures: Primary cell lines (short-lived), diploid cell lines (from human embryos, ~100 generations), and continuous cell lines (from cancer cells, e.g., HeLa cells, maintained indefinitely).

Viral Identification

• Cytopathic effects: Visible changes in infected cell cultures.

• Serological tests: ELISA detects viral antigens using antibodies.

• Nucleic acid tests: PCR amplifies and detects viral genetic material.

Viral Multiplication

One-Step Growth Curve

Viral replication follows a one-step growth curve, with an eclipse period (no detectable virions), followed by a sharp increase as virions are released from the host cell.

Multiplication of Bacteriophages

Bacteriophages multiply via two main mechanisms:

• Lytic cycle: Phage causes lysis and death of the host cell (e.g., T-even bacteriophages).

• Lysogenic cycle: Phage DNA integrates into host DNA as a prophage, replicating with the host cell without killing it immediately.

Outcomes of Lysogeny

• Lysogenic cells are immune to reinfection by the same phage.

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

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

Comparison: Bacteriophage vs. Animal Virus Multiplication

Stage	Bacteriophages	Animal Viruses
Attachment	Tail fibers attach to cell wall proteins	Receptor sites are plasma membrane proteins/glycoproteins
Entry	Viral DNA injected into host cell	Capsid enters by endocytosis or fusion
Uncoating	Not required	Enzymatic removal of capsid proteins
Biosynthesis	In cytoplasm	In nucleus (DNA viruses) or cytoplasm (RNA viruses)
Chronic Infection	Lysogeny	Latency; slow viral infections; cancer
Release	Host cell is lysed	Enveloped viruses bud out; nonenveloped viruses rupture plasma membrane

Multiplication of Animal Viruses

• Attachment: To cell membrane receptors.

• Entry: By receptor-mediated endocytosis or fusion.

• Uncoating: Separation of viral nucleic acid from capsid by enzymes.

• Biosynthesis: Production of viral nucleic acid and proteins.

• Maturation: Assembly of viral components.

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

Naked vs. Enveloped Viruses

• Naked viruses: More resistant to drying, heat, detergents, and acids; must kill host cells to be released.

• Enveloped viruses: Sensitive to environmental factors; released by budding; cannot survive GI tract; require moist transmission.

Biosynthesis of DNA and RNA Viruses

DNA Viruses

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

• Adenoviridae: dsDNA, nonenveloped; respiratory infections, tumors in animals.

• Poxviridae: dsDNA, enveloped; smallpox, vaccinia, MPOX; assembly in cytoplasm.

• Herpesviridae: dsDNA, enveloped; cold sores, chickenpox, mononucleosis, cytomegalovirus, roseola, Kaposi’s sarcoma.

• Papovaviricetes: dsDNA, nonenveloped; warts, some cause cancer.

• Hepadnaviridae: dsDNA, enveloped; hepatitis B, uses reverse transcriptase.

RNA Viruses

RNA viruses replicate in the cytoplasm using RNA-dependent RNA polymerase. Their genomes may be single-stranded (+ or − sense) or double-stranded.

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

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

• dsRNA: Double-stranded RNA genome.

• Coronaviridae: ssRNA (+), enveloped; includes SARS-CoV-2 (COVID-19).

• Togaviridae: ssRNA (+), enveloped; includes alphavirus (encephalitis), rubivirus (rubella).

• Rhabdoviridae: ssRNA (−), enveloped; includes rabies virus.

• Picornaviridae: ssRNA (+), nonenveloped; includes poliovirus, rhinovirus, hepatitis A.

• Reoviridae: dsRNA, nonenveloped; includes rotavirus (gastroenteritis).

Retroviruses

Retroviruses (e.g., HIV) are ssRNA viruses that use reverse transcriptase to produce DNA from their RNA genome. The DNA integrates into the host chromosome as a provirus, which is protected from the host immune system and antiviral drugs.

Viruses and Cancer

Oncogenic Viruses

Some viruses can cause cancer by integrating their genetic material into the host genome, leading to transformation of normal cells into tumor cells. Proto-oncogenes are normal genes that, when mutated, become oncogenes and drive uncontrolled cell growth.

• DNA oncogenic viruses: Adenoviridae, Herpesviridae (Epstein-Barr virus), Poxviridae, Papovaviridae (HPV), Hepadnaviridae (hepatitis B).

• RNA oncogenic viruses: Retroviridae (HTLV-1, HTLV-2, FeLV).

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

Latent and Persistent Viral Infections

Latent Infections

Latent viruses remain dormant in host cells for long periods, with no symptoms. They may reactivate due to changes in immunity. All herpesviruses are capable of latency (e.g., cold sores, shingles).

Persistent Infections

Persistent viral infections progress slowly over a long period and are often fatal (e.g., subacute sclerosing panencephalitis caused by measles virus).

Disease	Primary Effect	Causative Virus
Cold sores	Skin and mucous membrane lesions	HHV-1, HHV-2
Leukemia	Increased white blood cell growth	HTLV-1, HTLV-2
Shingles	Skin lesions	Varicellovirus
Cervical cancer	Increased cell growth	Human papillomavirus
HIV/AIDS	Decreased CD4+ T cells	HIV-1, HIV-2
Liver cancer	Increased cell growth	Hepatitis B virus
Progressive encephalitis	Mental deterioration	Rubella virus
SSPE	Mental deterioration	Measles virus

Viroids and Prions

Viroids

Viroids are infectious RNA molecules that cause disease in plants. They lack a protein coat and are much smaller than viruses.

Prions

Prions are infectious proteins that cause neurodegenerative diseases. They are inherited or transmissible by ingestion, transplant, or surgical instruments. Prion diseases include:

• Spongiform encephalopathies (e.g., mad cow disease, Creutzfeldt-Jakob disease, fatal familial insomnia, sheep scrapie).

• Normal cellular prion protein (PrPc) is converted into the infectious misfolded form (PrPSc), which accumulates in brain cells and forms plaques.

Additional info: The Baltimore classification system is widely used in virology to categorize viruses based on their genome type and replication strategy. Understanding the differences between latent and persistent infections is crucial for clinical management and epidemiology of viral diseases.