Viruses and Subviral Particles Notes

Viruses and Subviral Particles

• Viruses are acellular and thus do not fit into cell theory.
• Size:
  • Viruses: 20-300 nm
  • Prokaryotes: 1-10 μm
  • Eukaryotes: ~10x larger than prokaryotes
• Viruses lack organelles and a nucleus.

Viral Structure

• Composed of:
  • Genetic material (DNA or RNA, single or double-stranded, circular or linear)
  • Protein coat (capsid)
  • Sometimes an envelope (phospholipids and proteins which are biospecific).
• Envelopes are sensitive to heat, detergents, and desiccation, thus enveloped viruses are easier to kill.
• Non-enveloped viruses are more resistant and persist longer on surfaces.
• Viruses are obligate intracellular parasites because they cannot reproduce independently (lack ribosomes).
• They hijack host cell machinery to replicate and produce viral progeny.

Bacteriophages

• Viruses that target bacteria.
• Inject genetic material into the bacteria, leaving the rest of the structure outside.
• Structure includes:
  • Capsid
  • Tail sheath (injects genetic material)
  • Tail fibers (help recognize and connect to the correct host cell)

Viral Genomes

• Vary in size and shape.
• Made of single or double-stranded DNA or RNA.
• Single-stranded RNA viruses:
  • Positive-sense: genome can be directly translated to functional proteins (like mRNA).
  • Negative-sense: RNA strand acts as a template for synthesis of a complementary strand, which is then used for protein synthesis; requires RNA replicase in the virion.

Retroviruses

• Enveloped, single-stranded RNA viruses (family Retroveridae).
• Contain two identical RNA molecules.
• Carry reverse transcriptase, which synthesizes DNA from single-stranded RNA.
• DNA integrates into the host cell genome and is replicated and transcribed as if it were the host cell's own DNA.
• Allows indefinite infection; only way to remove infection is to kill the infected cell.
• HIV is an example; this mechanism makes it difficult to treat.

Viral Life Cycle

• Infection requires binding to specific receptors on the host cell.
• Envelope viruses fuse with the plasma membrane; otherwise, the host cell may bring in the virus via endocytosis.
• Bacteriophages use tail fibers to anchor and inject their genome using the tail sheath; some tail fibers have enzymatic activity for cell wall penetration.
• Entry:
  • Envelope viruses (e.g., HIV) fuse with the membrane and enter intact.
  • Bacteriophages inject genetic material only.

Translation and Progeny Assembly

• Viral genetic material must be translated for reproduction.
• DNA viruses enter the nucleus to be transcribed into mRNA, which then goes to the cytoplasm for translation.
• Positive-sense RNA viruses are translated directly in the cytoplasm.
• Negative-sense RNA viruses require RNA replicase to synthesize a complementary RNA strand for translation.
• DNA from retroviruses travels to the nucleus for integration into the host genome.
• Host cell ribosomes, tRNA, amino acids, and enzymes are used for protein synthesis.
• Structural capsid proteins are created, and viral genomes are packaged within the capsid.
• Retroviruses transcribe new copies of their single-stranded RNA from the DNA in the host genome.
• A single virus may create hundreds to thousands of new virions in a host cell.

Progeny Release

• Cell death: viral invasion initiates cell death and subsequent spilling of viral progeny.
• Cell lysis: host cell lysis occurs due to a large number of virions (disadvantageous because the virus can no longer use the cell).
• Extrusion: virus leaves by fusing with the plasma membrane (productive cycle, keeps host cell alive).

Lytic and Lysogenic Cycles

• Applies to bacteriophages.
• Lytic cycle: bacteriophage maximizes the use of the cell's machinery, causing lysis once full of virions; viruses are termed virulent in this phase.
• Lysogenic cycle: virus integrates into the host genome as a provirus or prophage and replicates along with the bacterium; environmental factors may cause reversion to a lytic cycle.
• The provirus may extract bacterial genes upon leaving the genome, allowing transduction.
• Provirus integration may benefit the bacterium by making it less susceptible to superinfection.

Prions and Viroids

• Subviral particles that can cause disease.
• Prions:
  • Infectious proteins (nonliving).
  • Cause disease by triggering misfolding of other proteins, converting them from $\alpha$-helical structure to $\beta$-pleated sheets.
  • Reduces solubility and the ability of the cell to degrade the protein, this causes protein aggregates to form, interfering with cell function.
  • Examples: bovine spongiform encephalopathy (mad cow disease), Creutzfeldt-Jakob disease, familial fatal insomnia.
• Viroids:
  • Small, circular, single-stranded RNA that infects plants.
  • Binds to RNA sequences and silences genes in the plant genome.
  • Prevents synthesis of necessary proteins, leading to metabolic disruption and structural damage.
  • Example: hepatitis D virus (HDV) in humans requires co-infection with HBV to exert its silencing effect on human hepatocytes.

Conclusion

• Viruses are nonliving infectious particles.
• Prions and viroids are the smallest infectious particles.

Vaccines

Vaccines are available for a number of bacteria and viruses including:

• Bacteria:
  • Bacillus anthracis (anthrax)
  • Corneobacterium (diphtheria)
  • Hemophilus influenza type b (many upper respiratory and ear infections)
  • Neisseria meningitidis (some cases of bacterial meningitis)
  • Streptococcus pneumonia (many cases of bacterial pneumonia)
  • Clostridium (tetanus)
  • Salmonella (typhoid)
  • Bordetella pertussis (whooping cough)
• Viruses:
  • Varicella-zoster virus (chickenpox and shingles)
  • Hepatitis A and B viruses
  • Human papillomavirus (HPV)
  • Influenza
  • Measles
  • Mumps
  • Polio
  • Rabies
  • Rotavirus
  • Rubella
  • Yellow fever

Antibiotic and antiviral therapies

Those for which we do not have vaccines may be targeted with antibiotic and antiviral therapies.
The appropriate pharmacotherapy usually depends on an understanding of bacterial or viral physiology and the known resistance patterns in the local area.

Cellular Reproduction

• Bacterial cells can reproduce by binary fission.
• Eukaryotic cells such as human cells reproduce using mitosis and meiosis.