Viruses and Prions: Structure, Classification, Replication, and Clinical Principles

Viruses and Prions

General Virus Characteristics

Viruses are submicroscopic, infectious agents that are classified as nonliving microbes. They are obligate intracellular pathogens, meaning they require a host cell to replicate. Virology is the study of viruses, and understanding viruses requires foundational knowledge in cellular biology.

• Size: Extremely small (30–1000 nm), acellular, and filterable.

• Host Range: About 270 viruses infect humans, with many more uncharacterized.

• Structure: Composed of a protein capsid and nucleic acid (DNA or RNA).

• Replication: Hijack host cell machinery for replication.

• Metabolism: Do not exhibit metabolism.

Characteristic	Viruses	Prokaryotes	Eukaryotes
Cells?	No	Yes	Yes
Considered alive?	No	Yes	Yes
Relative size	Smaller than prokaryotes	Bigger than viruses, smaller than eukaryotes	Bigger than prokaryotes and viruses
Structure	Protein capsid & nucleic acid	Cells without nuclei	Cells with nuclei
Replication	Host cell machinery	Binary fission	Mitosis/Meiosis
Metabolism	No	Yes	Yes
Genome	DNA or RNA	DNA	DNA

Viral Structure

Viruses exhibit diverse structural and genomic features. The infectious virus particle is called a virion, which consists of an exterior protective protein capsid and genetic material.

• Capsid: Protein shell made of capsomere subunits; protects the genome.

• Capsid Shapes: Helical (hollow tube), icosahedral (polygon), or complex.

Capsid protein shells are held together by hydrophobic binding, van der Waals forces, and salt bridges at specific binding domains.

Viral Envelopes and Spikes

Some viruses have a lipid-based envelope derived from the host cell membrane, while others are naked (non-enveloped). Animal viruses may be enveloped or naked; bacteriophages are always naked.

• Spikes (Peplomers): Glycoprotein extensions that facilitate attachment and entry into host cells; bind to specific host cell factors.

Influenza viruses mutate frequently, causing changes in spike proteins (Hemagglutinin [HA] and Neuraminidase [NA]), which define influenza subtypes (e.g., H1N1).

Viral Genomes

Viral genomes are highly variable and encode capsomere proteins, enzymes for replication, and structural factors. They can be DNA or RNA, single or double stranded, segmented or non-segmented, circular or linear.

• DNA Viruses: Often double stranded, may be single stranded, circular or linear.

• RNA Viruses: Often single stranded, may be double stranded, linear or segmented.

Making mRNA from Viral Genomes

Viruses must hijack host cell machinery to make viral proteins. The process of making mRNA varies by genome type:

• dsDNA viruses: Transcribed by host RNA polymerases.

• ssDNA viruses: Converted to dsDNA before transcription.

• ssRNA (+): Genome acts as mRNA, directly translated.

• ssRNA (–): Complementary to mRNA, transcribed by viral RNA-dependent RNA polymerases.

• Retroviruses: RNA genome converted to DNA by reverse transcriptase, then integrated and transcribed.

• dsRNA viruses: Transcribed to make mRNA by viral RNA-dependent RNA polymerases.

Viral Genome Evolution

Viruses change rapidly due to quick replication, large virion production, and high mutation rates (especially RNA viruses, which lack proofreading). Mutations can be neutral, beneficial, or deleterious.

• Attenuated Strains: Reduced virulence, used in vaccines.

• Reassortment: Occurs when two viral strains co-infect a cell, leading to new strains.

Antigenic Drift and Shift

Influenza viruses undergo antigenic drift (minor changes in HA/NA spikes due to mutations) and antigenic shift (major genetic reassortment, often leading to pandemics).

• Antigenic Drift: Minor changes, host may lose immunity.

• Antigenic Shift: Major changes, new highly virulent strains, no residual immunity.

Classifying and Naming Viruses

Classification Criteria

Viruses are classified by the International Committee on Taxonomy of Viruses (ICTV) based on:

• Type of nucleic acid (DNA or RNA)

• Capsid symmetry (helical, icosahedral, complex)

• Envelope presence

• Genome architecture (ssDNA, ssRNA, etc.)

Medically Important Virus Families

Examples of DNA and RNA virus families relevant to human health:

Family	Genome	Capsid	Envelope	Example
Papillomaviridae	dsDNA circular	Icosahedral	Naked	HPV
Herpesviridae	dsDNA linear	Icosahedral	Enveloped	HSV, VZV
Poxyviridae	dsDNA linear	Complex	Enveloped	Sm. pox virus
Flaviviridae	ssRNA+ Non-RT	Icosahedral	Enveloped	HEP C
Retroviridae	ssRNA+ RT	Icosahedral	Enveloped	HIV
Coronavirdae	ssRNA+	Helical	Enveloped	COVID-19
Paramyxovirdae	ssRNA-	Helical	Enveloped	Measles & Mumps
Orthomyxoviridae	ssRNA– segmented	Helical	Enveloped	Influenza

Host Range and Tropism

Host range is the collection of species a virus can infect; tropism is the tissue or cell specificity. Some viruses have broad tropism (Ebola), others have narrow tropism (HIV).

Virus Sizes

Viruses range from 30 nm (rhinovirus, poliovirus) to 1,500 nm (pithovirus). Pathogenic animal viruses are typically 30–1,000 nm.

Naming Conventions

Viruses are named using standardized rules, with the phylum as the highest taxon. Naming conventions include order, family, subfamily, genus, and species.

Viral Replication Pathways

Generalized Steps for Animal Virus Replication

Animal virus replication involves six steps:

1. Attachment: Virus binds to host cell via capsid proteins (non-enveloped) or spikes (non-enveloped & enveloped).

2. Penetration: Entry by endocytosis/membrane fusion (enveloped), or endocytosis (non-enveloped).

3. Uncoating: Capsid is digested in the endocytic vesicle/cytoplasm/nucleus, genome is released.

4. Replication (synthesis): Genome is replicated and viral proteins are made.

5. Assembly: New virions are formed.

6. Release: Enveloped viruses bud off; non-enveloped rupture/lyse the cell during release.

Persistent Infections

Some viruses cause persistent infections, which can be chronic (continuous release of virions and slow progression of disease) or latent (flare-ups with dormancy/latency). Examples include HIV & Provirus; integrated DNA (chronic) and herpesviruses (latent).

• Herpesviridae

  • Human herpes virus -1 (HSV-1): cold sores

  • HSV-2: genital herpes

  • Varicella-zoster virus (HHV-3): chickenpox and shingles

Oncogenic Viruses

Oncogenic viruses (oncoviruses) can cause cancer by stimulating uncontrolled cell division or reducing cell death signals.

Virus	Genome	Integrates DNA?	Cancer Link	Mechanism
HPV	DNA Papillomaviridae family	Yes	Cervical, oropharyngeal, and anal cancers	Uncontrolled cell division
Human herpes virus-8	DNA; Herpesviridae family	No	Kaposi sarcoma (skin cancer)	Uncontrolled cell division
Epstein-Barr (HHV-4 causes mononucleosis- kissing disease	DNA; Herpesviridae family	No	B-cell and T-cell lymphomas and Hodgkin's disease	Uncontrolled cell division
HTLV	RNA; Retroviridae family	Yes	Adult T-cell leukemia	Uncontrolled cell division
Hepatitis B	DNA; Hepadnaviridae family	No	Liver cancer	Chronic inflammation causes host cell DNA damage and mutations
Hepatitis C	RNA; Flaviviridae family	No	Liver cancer	Chronic inflammation causes host cell DNA damage and mutations

Clinical Aspects of Viruses

Laboratory Propagation

Viruses are propagated in the lab using cell culture, live animal hosts, or embryonated eggs. The plaque assay is used to quantify infectious viral particles (PFU/ml).

- clear zones are the plaques

Diagnostic Methods

Specificity: the test only detects the virus(es) of interest (no false positives)

Sensitivity: the test detects very low levels of the target (no false negetives)

Detection of viruses relies on molecular methods due to their small size. Key methods include:

• Agglutination Tests: Use antibodies or antigens linked to beads; positive result is agglutination (stick together).

• Enzyme-linked immunosorbent Assay (ELISA): Detects viral proteins or antibodies; color change indicates binding to surface.

• Nucleic Acid Detection: PCR and RT-qPCR (reads amplification RNA to DNA) detect viral genetic material with high sensitivity and specificity. (very good)

  • RT-qPCR results: "cycle threshold" (Ct)- number of cycles for the signal to reach the threshold where it can be seen over background signal

    • high concentration: low Ct number- don't need much amplification to see it

    • Low concentration: high Ct number- need a lot of amplification to see it

Antiviral Drugs

Antiviral drugs target various steps in viral replication but rarely cure infections. Most drugs target viral enzymes and must be selectively toxic. Vaccines are crucial for prevention.

• Attachment/Penetration/Uncoating Inhibitors: Block viral entry (e.g., amantadine, maraviroc).

• Replication Inhibitors: Nucleoside analogs (e.g., acyclovir (DNA), ribavirin (RNA)) block nucleic acid synthesis. Stop polymerase.

• Nucleoside reverse transcriptase inhibitors (NTRIs): target reverse transcriptase enzymes (e.g., Azidothymidine (AZT)).

• Interferons: Naturally occurring. Signal cells to make defensive changes; can be administered therapeutically.

• Release Inhibitors: Oseltamivir and zanamivir prevent influenza virion release.

Prions

Prion Structure and Diseases

Prions are infectious proteins with no genetic material; they do not replicate. They cause transmissible spongiform encephalopathies (TSEs), such as Creutzfeldt-Jakob disease and fatal familial insomnia.

• Gerstmann-Straussler-Schienker Syndrome- fatal familial insomnia inherited.

• Creuzfeldt-Jakob Disease (CJD)- acquired from cows

• Prion-like Disorders: Neurodegenerative diseases (Alzheimer's, Parkinson's, ALS) are associated with misfolded proteins.