Chapter 13: Characterizing and Classifying Viruses, Viroids, and Prions

General Characteristics and Basic Structure of Viruses

Viruses are acellular, obligate intracellular parasites that exist as inert macromolecules outside host cells and become active only upon entering a susceptible living cell.
Extracellular vs. Intracellular State:
- Extracellular State: The complete virus particle is termed a virion. It consists of a nucleic acid genome surrounded by a protective protein coat called a capsid. The combination of nucleic acid and capsid is known as a nucleocapsid. Some virions are enclosed within a phospholipid envelope. The outermost layer of the virion provides mechanical protection and contains surface recognition sites for attachment to host cell receptors.
- Intracellular State: Upon host cell entry, the capsid is removed, and the virus exists purely as intracellular nucleic acid.
Viral Genome Composition:
- Contains either DNA or RNA, but never both simultaneously.
- Genomes can be single-stranded (ssDNA or ssRNA) or double-stranded (dsDNA or dsRNA).
- Structural configuration may be linear or circular.
Capsid Structure:
- Built from repeating protein subunits known as capsomeres.
- Protects the viral nucleic acid from enzymatic degradation and environmental damage.
Envelope Structure:
- Acquired from host cell membranes during viral replication or budding release.
- Composed of a host-derived phospholipid bilayer intermixed with viral proteins.
- Glycoprotein spikes project outward from the envelope. These spikes are highly mutable, allowing viruses to evade host antibody responses and vaccine immunity.

Relative Dimensions of Biological Entities:
- Red blood cell diameter: $10000\,nm$
- Escherichia coli cell dimensions: $1000\,nm \times 3000\,nm$
- Smallpox virus (Orthopoxvirus): $200\,nm \times 300\,nm$
- Tobacco mosaic virus: $15\,nm \times 300\,nm$
- Bacteriophage T4: $50\,nm \times 225\,nm$
- Poliovirus: $30\,nm$
- Bacteriophage MS2: $24\,nm$
- Bacterial ribosome: $25\,nm$

Viral Morphology and Host Range

Structural Categories of Virions:
- Helical: Capsomeres bound in a spiral pattern forming a hollow, cylindrical tube enclosing the viral nucleic acid.
- Polyhedral: Geometrically symmetrical with multiple flat faces; most commonly icosahedral (20 triangular faces and 12 corners).
- Enveloped: Roughly spherical or pleomorphic outer shape resulting from the surrounding membrane, housing helical or polyhedral capsids internally.
- Complex: Capsids possess additional specialized structures attached (e.g., bacteriophages featuring complex head, tail sheath, base plate, and tail fibers).

Host Range Specificity:
- Viruses infect organisms across all domains of life (animals, plants, fungi, protists, bacteria, and archaea).
- Viruses that target bacteria are termed bacteriophages or phages.
- Host specificity is dictated by:
1. Precise chemical binding between viral surface attachment proteins and complementary host cell surface receptors.
2. Availability of appropriate cellular machinery within the host to produce viral progeny.
- Specificity and cell-lysing properties can be harnessed for therapeutic applications, such as targeting bacterial infections (phage therapy) or destroying malignant tumor cells (oncolytic virotherapy).

Taxonomy and Classification of Human Viruses

Classification Criteria: Taxonomy is based on nucleic acid type, presence or absence of an envelope, capsid symmetry, and virion size.
Taxonomic Hierarchy: Viruses are grouped into genera and families (family names end in -viridae). Broader phylogenetic relationships remain poorly resolved by taxonomists.
Sense of Single-Stranded RNA Genomes:
- Positive-sense (+RNA): Equivalent in sequence to viral mRNA; can be directly translated into proteins by host cell ribosomes.
- Negative-sense (-RNA): Complementary in sequence to mRNA; cannot be translated directly and must first be transcribed into +RNA by a viral RNA polymerase.
Complete Breakdown of Human Virus Families:

DNA Viruses

Poxviridae:
- Strand Type: Double-stranded DNA (dsDNA)
- Representative Genera & Diseases: Orthopoxvirus (smallpox)
Herpesviridae:
- Strand Type: Double-stranded DNA (dsDNA)
- Representative Genera & Diseases: Simplexvirus (herpes type 1: fever blisters, respiratory infections; herpes type 2: genital infections), Varicellovirus (chickenpox), Lymphocryptovirus / Epstein-Barr virus (infectious mononucleosis, Burkitt's lymphoma), Cytomegalovirus (birth defects), Roseolovirus (roseola)
Papillomaviridae:
- Strand Type: Double-stranded DNA (dsDNA)
- Representative Genera & Diseases: Papillomavirus (benign tumors, warts, cervical and penile cancers)
Polyomaviridae:
- Strand Type: Double-stranded DNA (dsDNA)
- Representative Genera & Diseases: Polyomavirus (progressive multifocal leukoencephalopathy)
Adenoviridae:
- Strand Type: Double-stranded DNA (dsDNA)
- Representative Genera & Diseases: Mastadenovirus (conjunctivitis, respiratory infections)
Hepadnaviridae:
- Strand Type: Partial single-stranded and partial double-stranded DNA
- Representative Genera & Diseases: Orthohepadnavirus (hepatitis B)
Parvoviridae:
- Strand Type: Single-stranded DNA (ssDNA)
- Representative Genera & Diseases: Erythrovirus (erythema infectiosum)

RNA Viruses

Picornaviridae:
- Strand Type: Single-stranded positive-sense RNA (+ssRNA)
- Representative Genera & Diseases: Enterovirus (polio), Hepatovirus (hepatitis A)
Caliciviridae:
- Strand Type: Single-stranded positive-sense RNA (+ssRNA)
- Representative Genera & Diseases: Norovirus (gastroenteritis)
Astroviridae:
- Strand Type: Single-stranded positive-sense RNA (+ssRNA)
- Representative Genera & Diseases: Astrovirus (gastroenteritis)
Hepeviridae:
- Strand Type: Single-stranded positive-sense RNA (+ssRNA)
- Representative Genera & Diseases: Hepevirus (hepatitis E)
Togaviridae:
- Strand Type: Single-stranded positive-sense RNA (+ssRNA)
- Representative Genera & Diseases: Alphavirus (encephalitis), Rubivirus (rubella)
Flaviviridae:
- Strand Type: Single-stranded positive-sense RNA (+ssRNA)
- Representative Genera & Diseases: Flavivirus (yellow fever, Japanese encephalitis), Hepacivirus (hepatitis C)
Coronaviridae:
- Strand Type: Single-stranded positive-sense RNA (+ssRNA)
- Representative Genera & Diseases: Coronavirus (common cold, severe acute respiratory syndrome [SARS])
Retroviridae:
- Strand Type: Single-stranded positive-sense RNA (+ssRNA), segmented
- Representative Genera & Diseases: Deltaretrovirus (leukemia), Lentivirus (AIDS)
Orthomyxoviridae:
- Strand Type: Single-stranded negative-sense RNA (-ssRNA), segmented
- Representative Genera & Diseases: Influenzavirus (flu)
Paramyxoviridae:
- Strand Type: Single-stranded negative-sense RNA (-ssRNA)
- Representative Genera & Diseases: Paramyxovirus (common cold, respiratory infections), Pneumovirus (pneumonia, common cold), Morbillivirus (measles), Rubulavirus (mumps)
Rhabdoviridae:
- Strand Type: Single-stranded negative-sense RNA (-ssRNA)
- Representative Genera & Diseases: Lyssavirus (rabies)
Bunyaviridae:
- Strand Type: Single-stranded negative-sense RNA (-ssRNA), segmented
- Representative Genera & Diseases: Bunyavirus (California encephalitis virus), Hantavirus (pneumonia)
Filoviridae:
- Strand Type: Single-stranded negative-sense RNA (-ssRNA)
- Representative Genera & Diseases: Filovirus (Ebola hemorrhagic fever), Marburgvirus (hemorrhagic fever)
Arenaviridae:
- Strand Type: Single-stranded negative-sense RNA (-ssRNA), segmented
- Representative Genera & Diseases: Lassavirus (hemorrhagic fever)
Reoviridae:
- Strand Type: Double-stranded RNA (dsRNA), segmented
- Representative Genera & Diseases: Orbivirus (encephalitis), Rotavirus (diarrhea), Coltivirus (Colorado tick fever)

Bacteriophage Replication Cycles

The two primary pathways of bacteriophage replication are the Lytic Cycle (resulting in host cell lysis and death) and the Lysogenic Cycle (where the host cell remains viable while harboring latent viral genetic material).

The Lytic Replication Cycle

Attachment: Phage tail fibers attach precisely to complementary receptor sites on the host bacterial cell wall.
Entry (Penetration): The phage releases lysozyme to degrade peptidoglycan in the cell wall. The tail sheath contracts, driving a hollow tube through the outer membrane and cell wall to inject the phage genome directly into the host cytoplasm. The protein capsid remains exterior to the cell.
Synthesis: Host cell enzymes degrade host chromosomal DNA. The virus hijacks host ribosomes and metabolic machinery to transcribe viral mRNA, replicate the phage genome, and translate structural phage proteins (capsid, tail sheath, base plate, tail fibers).
Assembly: Spontaneous self-assembly of viral components into mature head structures, tail sheaths, base plates, and tail fibers to produce complete virions.
Release: Lysozyme synthesized inside the host cell hydrolyzes the peptidoglycan cell wall from within. The weakened bacterial cell wall ruptures under osmotic pressure, lysing the bacterial host cell and releasing new infective virions.

Lytic Replication Cycle in Bacteriophages

The Lysogenic Replication Cycle

Attachment & Entry: A temperate phage (e.g., Lambda phage) attaches and injects its genome into the bacterial cell.
Prophage Formation: The injected linear viral DNA circularizes and integrates directly into the host bacterial chromosome using viral enzymes, becoming a prophage.
Lysogenic Cell Division: The bacterial cell survives and replicates its own chromosome, simultaneously copying the integrated prophage. All daughter cells inherit the latent viral genome.
Induction: Physical or chemical environmental stressors (e.g., ultraviolet light, DNA-damaging agents) trigger the prophage to excise itself from the bacterial chromosome.
Re-entry into Lytic Cycle: Once excised, the viral genome initiates the lytic cycle steps: synthesis of viral components, assembly, and host lysis.

Lysogenic Replication Cycle in Bacteriophages

Consequences of Lysogeny

Immunity to Superinfection: Lysogenic cells become immune to secondary infection by the same or closely related phage types.
Lysogenic / Phage Conversion: The presence of the prophage alters the bacterial phenotype, often conferring pathogenic traits such as diphtheria toxin production (Corynebacterium diphtheriae), cholera toxin production (Vibrio cholerae), or botulinum toxin production (Clostridium botulinum).
Specialized Transduction: During induction, the excised prophage improperly detaches, carrying adjacent host bacterial genes with it (e.g., the galactose utilization gene gal). When the newly packaged phage infects a recipient cell, it transfers the host gene, conferring new metabolic capabilities to the recombinant host.

Replication Strategies of Animal Viruses

Animal virus multiplication involves six steps: Attachment, Entry, Uncoating, Synthesis, Maturation (Assembly), and Release.

1. Attachment

Driven by chemical attraction between viral attachment structures (glycoprotein spikes or capsid proteins) and host cell surface receptors (proteins or glycoproteins).

2. Entry Mechanisms

Direct Penetration: Sinking of naked virion capsids into the host membrane, creating a pore through which only the viral genome enters the cytoplasm while the capsid remains attached to the exterior membrane.
Membrane Fusion: Enveloped viruses fuse their lipid envelope directly with the host cell plasma membrane. The nucleocapsid enters the host cytoplasm, while the viral envelope and its glycoproteins remain integrated in the host cytoplasmic membrane.
Endocytosis: Host cell cytoplasmic membrane engulfs the entire virion (naked or enveloped) within an endocytic vesicle/endosome.

Three Mechanisms of Entry in Animal Viruses

3. Uncoating

Enzymatic removal of the viral protein capsid inside host vesicles or cytoplasm, exposing the viral nucleic acid.
The eclipse period represents the phase during which intact, infectious virions cannot be recovered from the host cell because the virions have disassembled.

4. Synthesis Strategies based on Genome Type

Double-Stranded DNA (dsDNA):
- Genomic replication occurs in the host nucleus using host DNA polymerase (each DNA strand serves as a template for its complement). Exception: Hepatitis B virus synthesizes RNA intermediate to act as the template for new DNA.
- Transcription of mRNA is performed by host RNA polymerase in the nucleus (or viral RNA polymerase in the cytoplasm for poxviruses).
- Capsid and functional proteins are translated by host ribosomes in the cytoplasm and transported back into the nucleus for assembly.
Single-Stranded DNA (ssDNA):
- Translocated to host nucleus, where host DNA polymerase synthesizes a complementary DNA strand to form dsDNA.
- Host RNA polymerase transcribes mRNA from the newly formed dsDNA template.
Positive-Sense Single-Stranded RNA (+ssRNA):
- The genomic +ssRNA functions directly as mRNA and is translated by host ribosomes into viral proteins, including viral RNA-dependent RNA polymerase.
- A complementary -ssRNA strand is synthesized to serve as a template for producing additional copies of genomic +ssRNA.
Negative-Sense Single-Stranded RNA (-ssRNA):
- Virions carry a pre-packaged enzyme called RNA-dependent RNA transcriptase.
- Upon entry, transcriptase uses -ssRNA to synthesize complementary +ssRNA, which acts both as mRNA for protein translation and as a template for manufacturing new genomic -ssRNA.
Double-Stranded RNA (dsRNA):
- Unwinds inside host cytoplasm. The positive strand acts as mRNA for protein synthesis.
- Each individual strand serves as a template for synthesizing its complementary strand using viral RNA polymerase.
Retroviridae (+ssRNA Retroviruses):
- Virions contain reverse transcriptase, integrase, and protease enzymes.
- Reverse transcriptase copies the +ssRNA genome into a complementary cDNA strand and then forms a dsDNA molecule.
- The dsDNA is transported into the nucleus, where integrase inserts it permanently into a host chromosome, forming a provirus.
- Host RNA polymerase transcribes the provirus into viral mRNA and genomic +ssRNA. Polyprotein precursors are processed and cleaved by viral protease.

Synthesis of Proteins and Genomes in Animal RNA Viruses

Multiplication Processes of Retroviridae

5. Assembly and Release

Site of Assembly: Most DNA viruses assemble within the host nucleus; most RNA viruses assemble entirely within the host cytoplasm.
Budding (Enveloped Viruses):
- Viral matrix proteins and glycoprotein spikes insert into host cell membranes.
- Assembled capsids push outward against membrane regions, becoming enclosed in host membrane buds. The host cell remains intact initially, permitting persistent, long-term release of virions.
Exocytosis or Lysis (Naked Viruses):
- Non-enveloped virions accumulate in host cells and are released via exocytosis or by inducing cell lysis (rupture), causing host cell death.

Comparative Summary: Bacteriophage vs. Animal Virus Replication

Attachment Structures:
- Bacteriophages: Tail proteins bind to protein receptors on bacterial cell walls.
- Animal Viruses: Spikes, capsid proteins, or envelope glycoproteins bind to proteins or glycoproteins on animal cell membranes.
Penetration Methods:
- Bacteriophages: Viral genome is injected directly into cytoplasm; capsid remains exterior.
- Animal Viruses: Entire capsid enters cell via direct penetration, membrane fusion, or endocytosis.
Uncoating Step:
- Bacteriophages: Absent (uncoating is unnecessary as capsid never enters cell).
- Animal Viruses: Required; capsid is digested by host or viral enzymes.
Site of Biosynthesis & Assembly:
- Bacteriophages: Entirely within host cytoplasm.
- Animal Viruses: RNA viruses synthesize and assemble in cytoplasm; most DNA viruses synthesize and assemble in nucleus.
Release Mechanisms:
- Bacteriophages: Lysis caused by viral lysozyme degradation of cell wall.
- Animal Viruses: Naked virions release via exocytosis or cell lysis; enveloped virions release via budding.
Nature of Chronic / Long-Term Infection:
- Bacteriophages: Lysogeny; viral DNA incorporates as a prophage, which can excise.
- Animal Viruses: Latency; viral DNA persists as a provirus (with or without chromosomal integration). Integration into host DNA is permanent.

Viral Growth Patterns, Infection Types, and Oncogenesis

Infection Dynamics:
- Acute Infection: Characterized by sudden onset, high peak virion production, rapid tissue damage, and complete viral clearance or host mortality within days.
- Latent Infection: Virions remain inactive within host tissues for extended periods without producing symptoms or infectious virus particles. Viral genetic material persists as a permanent provirus; activation can re-trigger acute symptoms later in life (e.g., Herpes simplex, Varicella-zoster virus).
- Persistent Infection: Virion production builds up gradually over months or years, maintaining continuous low-level viral release that eventually results in fatal tissue damage.
Virion Abundance (One-Step Growth Curve):
- Eclipse Phase: Virions enter cells, uncoat, and initiate synthesis; no extracellular virions are detectable in medium.
- Burst / Release Phase: Assembled virions escape cells via lysis or budding, resulting in a step-wise increase in infective virion concentration.
Viruses and Cancer (The Oncogene Theory):
- Viruses cause $20\%\text{--}25\%$ of all human cancers.
- Host genes that regulate normal cell growth and cell division are called protooncogenes.
- Factors that activate protooncogenes into oncogenes cause uncontrolled cell division, forming malignant tumors.
- Two-Hit Model of Viral Oncogenesis:
- First Hit: Virus integrates a promoter region upstream of a host protooncogene, converting it into an active oncogene. Host cell division remains controlled if a repressor gene continues to express functional repressor protein.
- Second Hit: Virus integrates into and disrupts the repressor gene locus. With repressor protein synthesis blocked, the oncogene product drives unrestricted cell division, causing cancer.
- Viral Associations with Human Cancers:
- Epstein-Barr virus: Burkitt's lymphoma and Hodgkin's disease
- Human herpesvirus 8 (HHV-8): Kaposi's sarcoma
- Human Papillomavirus (HPV): Cervical cancer and penile cancer

Laboratory Culture and Identification Methods

Viruses cannot be grown in standard acellular growth media (nutrient broth or agar); they require living host cells.

Culturing Bacteriophages

Liquid Cultures: Bacterial suspensions inoculated with phages clear as host cells lyse.
Solid Agar Lawns: Phages mixed with bacteria in top agar and poured over nutrient agar plates. Infection and lysis of contiguous bacteria generate clear, circular zones called plaques on the opaque bacterial lawn.
Concentration of viral stock is measured as Plaque-Forming Units (PFU).

Culturing Animal Viruses

Living Animals: Inoculation of laboratory hosts (mice, rabbits, primates).
Embryonated Chicken Eggs: Sterile, self-contained environment with isolated membranes for specific viral tropisms:
- Chorioallantoic membrane injection: For poxviruses.
- Amniotic injection: For influenza virus growth.
- Yolk sac injection: For specific intracellular agents and viruses.
- Allantoic cavity / Chorioallantois injection.

Inoculation Sites in Embryonated Chicken Eggs

Cell Culture Techniques:
1. Tissue samples are treated with proteolytic enzymes (e.g., trypsin) to dissociate individual cells.
2. Cells are suspended in specialized liquid nutrient media and transferred to culture flasks.
3. Normal cells attach to glass or plastic containers, forming a uniform monolayer across the surface.
4. Types of Cell Lines:
- Primary Cell Cultures: Extracted directly from host tissues; survive only $15\text{--}20$ passages.
- Diploid Cell Cultures: Derived from embryonic human/animal cells; survive roughly $50$ passages before dying.
- Continuous Cell Cultures: Derived from transformed or cancerous cells (e.g., HeLa cells); immortal, dividing indefinitely across infinite passages.
1. Viral multiplication in cell culture induces observable host structural damage known as the Cytopathic Effect (CPE).

Diagnostic Techniques for Identification

Visualization: Transmission Electron Microscopy (TEM) to determine particle size and capsid symmetry.
Serological Testing: Utilization of specific antibodies to detect viral antigens (e.g., ELISA, Western blot, neutralization tests).
Cytopathic Effect Analysis: Microscopic assessment of host cell morphological changes.
Molecular Diagnostics: Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) to amplify and identify viral nucleic acid sequences.

Subviral Pathogens: Viroids and Prions

Viroids

Characteristics: Extremely small, infectious circular pieces of single-stranded RNA (+ssRNA) that infect plants.
Dimensions: Approximately $2\,nm$ in width and $40\text{--}130\,nm$ in length.
Structure: Complete lack of a protein capsid ("naked" RNA). Viroid RNA contains no open reading frames and does not code for any proteins.
Pathogenesis: Viroid RNA contains sequences complementary to host plant mRNA. Upon infection, viroid RNA base-pairs with plant mRNA, forming double-stranded RNA complexes. Plant cellular endonucleases recognize dsRNA as foreign and degrade the complex, silencing essential plant genes and inducing pathology.
Plant Diseases & Manifestations: Potato Spindle Tuber Viroid (PSTVd) causes stunted growth, tuber deformation, color changes, and plant wilting.
Transmission: Requires entry through mechanical plant wounds (insect feeding, pruning tools, agricultural machinery) or via infected pollen.

Prions

Characteristics: Proteinaceous Infectious Particles ( $5\,nm \times 5\,nm$ ); devoid of nucleic acid (contain no DNA or RNA).
Pathology: Cause Transmissible Spongiform Encephalopathies (TSEs), progressive neurodegenerative diseases characterized by neuron death and formation of large vacuoles in brain tissue, imparting a sponge-like appearance.
Prion Protein (PrP) Structural Conformations:
- Cellular PrP (c-PrP): Normal, functional membrane glycoprotein synthesized by host cells and anchored to neuronal plasma membranes. Structure is rich in $\alpha$ -helices.
- Prion PrP (p-PrP): Disease-causing, infectious misfolded isoform. Structure is converted predominantly into $\beta$ -pleated sheets.

Mechanism of Prion Replication (Templating Action):
1. Host cells synthesize normal $\text{c-PrP}$ , which translocates to the cytoplasmic membrane.
2. Infectious $\text{p-PrP}$ enters host tissue via ingestion, tissue transplantation, contact of mucous membranes with infected material, or spontaneously due to a mutation in the host $\text{c-PrP}$ gene.
3. Infectious $\text{p-PrP}$ binds directly to cellular $\text{c-PrP}$ on the host cell surface.
4. $\text{p-PrP}$ acts as a conformational template, refolding host $\text{c-PrP}$ $\alpha$ -helices into $\text{p-PrP}$ $\beta$ -pleated sheets.
5. Newly generated $\text{p-PrP}$ converts additional $\text{c-PrP}$ molecules in an exponential chain reaction. The insoluble $\text{p-PrP}$ accumulates in the brain, forming aggregate plaques that lyse neurons.

Normal vs. Spongiform Encephalopathy Brain Tissue Histology

Prion Diseases:
- Human TSEs: Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, Fatal Familial Insomnia (FFI), Kuru.
- Animal TSEs: Scrapie (sheep and goats), Transmissible Mink Encephalopathy, Chronic Wasting Disease (CWD in deer and elk), Bovine Spongiform Encephalopathy (BSE or "Mad Cow Disease").
Physicochemical Resistance: Prions are resistant to standard autoclaving, boiling, ultraviolet radiation, ionizing radiation, and nucleases. They are inactivated only by extreme heat (incineration), autoclaving at high temperatures in concentrated sodium hydroxide ( $\text{NaOH}$ ), or specialized protease treatments. No effective therapeutic cure exists.

Comparative Matrix of Acellular Infectious Agents and Bacteria

Bacteria:
- Width: $200\text{--}2000\,nm$
- Length: $200\text{--}550000\,nm$
- Nucleic Acid: Contains both DNA and RNA
- Protein Content: Present
- Cellular Structure: Yes
- Cytoplasmic Membrane: Present
- Functional Ribosomes: Present
- Growth / Cell Division: Present
- Self-Replication Capacity: Yes (via binary fission/mitosis/sexual reproduction)
- Responsiveness to Environment: Present
- Metabolic Activity: Present
Viruses:
- Width: $10\text{--}400\,nm$
- Length: $20\text{--}800\,nm$
- Nucleic Acid: Either DNA or RNA, never both
- Protein Content: Present (capsid protein coat)
- Cellular Structure: No (acellular)
- Cytoplasmic Membrane: Absent (some possess host-derived membranous envelopes)
- Functional Ribosomes: Absent
- Growth / Cell Division: Absent
- Self-Replication Capacity: No (replicate via assembly-line manner using host machinery)
- Responsiveness to Environment: Limited (some bacteriophages respond to host cells by injecting genomes)
- Metabolic Activity: Absent
Viroids:
- Width: $2\,nm$
- Length: $40\text{--}130\,nm$
- Nucleic Acid: RNA only (+ssRNA)
- Protein Content: Absent
- Cellular Structure: No (acellular)
- Cytoplasmic Membrane: Absent
- Functional Ribosomes: Absent
- Growth / Cell Division: Absent
- Self-Replication Capacity: No
- Responsiveness to Environment: Absent
- Metabolic Activity: Absent
Prions:
- Width: $5\,nm$
- Length: $5\,nm$
- Nucleic Acid: None
- Protein Content: Present (PrP protein only)
- Cellular Structure: No (acellular)
- Cytoplasmic Membrane: Absent
- Functional Ribosomes: Absent
- Growth / Cell Division: Absent
- Self-Replication Capacity: No (transforms pre-existing host $\text{c-PrP}$ into $\text{p-PrP}$ )
- Responsiveness to Environment: Absent
- Metabolic Activity: Absent