Introduction to Viruses, Viroids, and Prions Practice Flashcards

The Search for the Elusive Virus

• Historical Pathogen Identification:

  • Robert Koch discovered the pathogens responsible for tuberculosis, cholera, and anthrax.

  • Friedrich Loeffler and Paul Frosch (1898): Identified a "filterable agent" as the cause of certain diseases, marking the early discovery of viruses.

Viruses in the Biological Spectrum

• Origins and Prevalence:

  • There is no universal agreement on the specific timeline or mechanism of viral origin.

  • Viruses are more numerous than all other cellular life forms on Earth combined.

  • They have played a fundamental role in the evolutionary trajectory of Bacteria, Archaea, and Eukarya.

• Definition: Viruses are characterized as obligate intracellular parasites.

Properties of Viruses (Exhaustive Characteristics)

• Biological Status:

  • Obligate intracellular parasites affecting bacteria, protists, fungi, plants, and animals.

  • Do not independently fulfill the fundamental characteristics of life (e.g., independent metabolism, growth, or reproduction outside a host).

  • Inactive macromolecules when outside the host cell; active only upon entering the host.

• Physical Attributes:

  • Size: Ultramicroscopic; typical range is between $20\,nm$ and $750\,nm$ in diameter. Most are less than $0.2\,\mu m$ and require an electron microscope to be seen.

  • Structure: Compact and economical; non-cellular in nature.

  • Symmetry: Crystalline nature due to regular, repeating molecular subunits. When purified, they can form large aggregates or crystals.

• Genetics and Metabolism:

  • Structure consists of a protein shell (capsid) surrounding a nucleic acid core.

  • Genome contains either DNA or RNA, but never both.

  • Nucleic acid configurations include double-stranded DNA ($dsDNA$), single-stranded DNA ($ssDNA$), single-stranded RNA ($ssRNA$), or double-stranded RNA ($dsRNA$).

  • Lack enzymes for most metabolic processes.

  • Lack protein synthesis machinery (ribosomes).

• Mechanism of Action:

  • Surface molecules impart high specificity for attachment to host cell receptors.

  • They multiply by hijacking the host cell's genetic material and directing it to synthesize and assemble new viral particles.

Viral Sizes and Giant Viruses

• Representative Sizes:

  • Mimivirus: $500\,nm$

  • Poxvirus: $400\,nm$

  • Herpes simplex: $150\,nm$

  • Rabies: $125\,nm$

  • HIV: $110\,nm$

  • Influenza: $100\,nm$

  • Adenovirus: $75\,nm$

  • T2 bacteriophage: $65\,nm$

  • Poliomyelitis: $30\,nm$

  • Yellow fever: $22\,nm$

  • Hemoglobin molecule (for scale): $15\,nm$

• Comparative Biological Sizes:

  • Red blood cells: $8\,\mu m$

  • Streptococcus: $1\,\mu m$ wide.

  • Escherichia coli: $2\,\mu m$ long.

• The Large Viruses (Giant Viruses):

  • Average $400$ to $1,500\,\mu m$ (representing 20 to 50 times the size of average viruses).

  • Named examples: Mimiviruses, Megaviruses, Pandoraviruses, and Pithoviruses.

Viral Structure and Components

• The Viral Particle (Virion):

  • Covering: Always includes a Capsid; may include an Envelope (not present in all viruses).

  • Central Core: Contains Nucleic acid molecules (DNA or RNA) and occasionally accessory Matrix proteins or Enzymes.

• Capsid types:

  • Nucleocapsid: The combined unit of the protein capsid and the nucleic acid.

  • Naked Viruses: Consist only of a nucleocapsid.

  • Enveloped Viruses: Possess an external covering acquired from the host cell membrane.

  • Capsomers: Identical protein subunits that assemble to form the capsid.

• Capsid Morphologies:

  • Helical: A continuous helix of capsomers forming a cylindrical nucleocapsid. Assembly involves rod-shaped capsomers forming hollow discs; nucleic acid is inserted and coiled as the structure elongates.

  • Icosahedral: A three-dimensional, symmetrical polygon with 20 sides and 12 evenly spaced corners. Nucleic acid is packed into the center.

• Viral Envelope and Spikes:

  • Predominantly found in animal viruses.

  • Acquired during the exit (budding) from the host cell.

  • Spikes: Exposed proteins on the outside of the envelope essential for attachment to host cell receptors.

• Functions of the Covering:

  • Protection of nucleic acid outside the host.

  • Binding to cell surfaces.

  • Facilitation of penetration/injection of viral genetic material.

• Complex/Atypical Viruses:

  • Poxviruses: Lack a typical capsid; covered by a dense layer of lipoproteins and coarse fibrils.

  • Bacteriophages: Often have a polyhedral nucleocapsid, a helical tail, and attachment fibers (tail pins/fibers that resemble spider legs).

Viral Genetics and Content

• Viral Genome: Carries only the genes necessary to invade the host and redirect its activity. Gene count ranges from a few to several thousand.

• Enzymes for Replication:

  • Polymerases: Synthesize DNA or RNA.

  • Replicases: Copy RNA.

  • Reverse transcriptase: Synthesizes DNA from an RNA template (e.g., HIV).

• RNA Genomes:

  • Positive-sense RNA ($+ssRNA$): Ready for immediate translation into proteins.

  • Negative-sense RNA ($-ssRNA$): Must be converted into the positive-sense form before translation.

  • Segmented RNA: The genome is divided into separate RNA pieces.

Viral Classification and Nomenclature

• Criteria: Structure, chemical composition, and genetic makeup.

• Current Statistics (ICTV): 59 orders, 189 families, and 2,224 genera.

• Naming Conventions:

  • Families: Italicized, suffix -viridae.

  • Genera: Italicized, suffix -virus.

  • Viral Species: Groups sharing host range, pathogenicity, and genetic makeup.

• Naming Bases:

  • Microscopic appearance (e.g., rhabdoviruses).

  • Anatomical/Geographic areas (e.g., adenoviruses, hantaviruses).

  • Effects on the host (e.g., lentiviruses).

  • Acronyms (e.g., picornaviruses).

Important Human Viral Families

DNA Viruses (Table 6.2a)

• Poxviridae: Orthopoxvirus (Variola/Vaccinia) - Smallpox, cowpox.

• Herpesviridae:

  • Simplexvirus - Fever blisters, cold sores (HSV-1), genital herpes (HSV-2).

  • Varicellovirus - Chickenpox, shingles (VZV).

  • Cytomegalovirus - CMV infections.

• Adenoviridae: Mastadenovirus - Adenovirus infection.

• Papillomaviridae: Papillomavirus - Several types of warts (HPV).

• Polyomaviridae: Polyomavirus - Progressive multifocal leukoencephalopathy (JC virus).

• Hepadnaviridae: Hepadnavirus - Serum hepatitis (Hepatitis B).

• Parvoviridae: Erythrovirus - Erythema infectiosum (Parvovirus B19).

RNA Viruses (Table 6.2b)

• Picornaviridae:

  • Enterovirus (Poliovirus, Coxsackievirus) - Poliomyelitis, Hand-foot-mouth disease.

  • Hepatovirus - Short-term hepatitis (Hepatitis A).

  • Rhinovirus - Common cold.

• Caliciviridae: Calicivirus (Norwalk virus) - Viral diarrhea.

• Togaviridae:

  • Alphavirus - Equine encephalitis.

  • Rubivirus - Rubella (German measles).

• Flaviviridae: Flavivirus - Dengue fever, West Nile fever, Zika fever.

• Bunyaviridae:

  • Bunyavirus - California encephalitis.

  • Hantavirus - Respiratory syndrome.

• Filoviridae: Filovirus - Ebola, Marburg fever.

• Reoviridae:

  • Coltivirus - Colorado tick fever.

  • Rotavirus - Gastroenteritis.

• Orthomyxoviridae: Influenzavirus - Influenza (Flu).

• Paramyxoviridae:

  • Paramyxovirus - Mumps, parainfluenza.

  • Morbillivirus - Measles.

  • Pneumovirus - Respiratory syncytial virus (RSV).

• Rhabdoviridae: Lyssavirus - Rabies (hydrophobia).

• Retroviridae:

  • Oncornavirus - T-cell leukemia (HTLV).

  • Lentavirus - AIDS (HIV).

• Arenaviridae: Arenavirus - Lassa fever.

• Coronaviridae: Coronavirus - Bronchitis, Enteritis, SARS, MERS, COVID-19 (SARS-CoV-2).

Animal Virus Multiplication Cycle

1. Adsorption: Specific binding of viral spikes to host cell receptors. Host range depends on this specificity:

   • Hepatitis B: Human liver cells.

   • Poliovirus: Primate intestinal and nerve cells.

   • Rabies: Various cells in many mammals.

2. Penetration: Entry into the host via:

   • Fusion: (Enveloped viruses) Envelope lipids fuse with the host membrane.

   • Endocytosis: (Enveloped or naked) The cell engulfs the virus into a vesicle/endosome.

3. Uncoating: Release of nucleic acid from the capsid into the cytoplasm.

4. Synthesis: Production of viral parts.

   • DNA viruses generally replicate/assemble in the nucleus.

   • RNA viruses generally replicate/assemble in the cytoplasm.

5. Assembly: Viral components (nucleocapsid, spikes) are put together. Capsids are often formed empty then filled with nucleic acid.

6. Release:

   • Budding/Exocytosis: (Enveloped) Nucleocapsid binds to the membrane, which pinches off. The cell is not immediately destroyed.

   • Lysis/Rupturing: (Nonenveloped/Complex) Viruses are released when the cell dies and bursts.

Effects on the Host Cell

• Cytopathic Effects (CPE): Microscopic cell damage.

  • Cell rounding (Smallpox, Influenza).

  • Inclusion bodies (cytoplasmic or nuclear mass/clumping).

  • Syncytium: Fusion of cells into large, multinucleated giant cells (Herpesvirus, Measles).

  • Negri bodies: Specific cytoplasmic inclusions in Rabies.

• Persistent Infections: The cell harbors the virus without immediate lysis.

  • Chronic Latent State: Periodic reactivation (e.g., Herpes simplex cold sores, Herpes zoster shingles).

• Transformation (Oncogenesis): Integration of viral DNA into host DNA, leading to cancer.

  • Transformed cells have increased growth rates and altered chromosomes.

  • Oncoviruses: Papillomavirus (cervical cancer), Epstein-Barr virus (Burkitt’s lymphoma).

Bacteriophages (Phage Therapy and Mechanics)

• Structure: Most studied are those infecting E. coli (T-even phages); contain DNA in an icosahedral head.

• Lytic Cycle Stages: Adsorption, Penetration (injection of DNA only; no uncoating), Replication, Assembly, Maturation, Lysis/Release.

• Lysogeny:

  • Temperate Phages undergo adsorption/penetration but do not replicate immediately.

  • Prophage: Inactive viral DNA inserted into the bacterial chromosome.

  • Induction: Activation of the prophage to enter the lytic cycle.

• Lysogenic Conversion: Bacteria acquire new traits (like toxins) from phage DNA.

  • Corynebacterium diphtheriae (Diphtheria toxin).

  • Vibrio cholerae (Cholera toxin).

  • Clostridium botulinum (Botulism toxin).

Cultivating and Identifying Animal Viruses

• Primary Goals: Isolation for identification, vaccine preparation, and research into structure/genetics.

• Methods:

  • In vitro (Cell/Tissue Cultures): Growth in petri dishes/flasks to observe CPEs.

  • In vivo (Bird Embryos): Use of amniotic, allantoic, or yolk sacs in intact units (e.g., chicken eggs).

  • In vivo (Live Animal Inoculation): Injection into skin, muscle, brain, or blood of laboratory animals.

Prions and Non-Viral Infectious Agents

• Prions: Infectious misfolded proteins containing no nucleic acid. Extremely resistant to sterilization.

  • Cause Transmissible Spongiform Encephalopathies (TSE): Fatal neurodegenerative diseases.

  • Animal examples: Scrapie (sheep/goats), BSE (Mad Cow), Wasting disease (elk).

  • Human example: Creutzfeldt-Jakob Syndrome (CJS).

• Satellite Viruses: Require a "helper" virus to replicate.

  • Adeno-associated virus (needs Adenovirus).

  • Delta agent (needs Hepatitis B).

• Viroids: Short pieces of naked RNA (no protein coat). Identified only in plants.

Robert Koch came up with germ theory, the idea that a single microorganism causes disease.