Virology

• Viruses are unique infectious agents which are very small (20 nm – 1500 nm). They consist of nucleic acids surrounded by protein coats, and some have envelopes. They contain only one type of nucleic acid, either DNA or RNA, and are dependent on living cells for replication.
• Viral genomes are smaller than prokaryotic cells, 2- 200kbp and usually linear, occasionally circular. They are often classified according to the genome and whether it's double or single stranded.
• A virion is a fully assembled infective virus. A nucleoprotein core can infect and replicate in host cell. Virion structure is one criteria for species classification.
• Capsids are a protein shell that encloses a viral genome formed of subunits composed of folded polypeptides. These subunits collectively form a structural unit (protomer) which then form assembly units.
• ' Capsomer ' describes features on a virus surface that correspond to protein subunits arranged around an axis of symmetry. They have a variable morphology based on the symmetry of the protein interface:

  • Helical (rod shape) e.g. TBV
  • Icosahedral (polyhedron shape) e.g. adenovirus
• Some viruses have viral envelopes which are made of a lipid bilayer and glycoproteins and acquired when nucleocapsids bud through the cell membrane. Some acquire an envelope from proteins encoded by a viral nucleic acid and incorporated as glycoprotein.
• “Spikes” on a viral envelope develop for some viruses, which are oligomers of surface glycoproteins.
• Viruses can only multiply within a host cell and only have limited composition. They require machinery of host cell to replicate such as the organelles, enzymes, and other macromolecules. The effect of viral replication on the host cell is variable.
• Host range: Each virus infects cells of a limited number of host species.
• Tissue tropism: Virus may have preference for cell type.
• Replication Cycle of a Virus:

  A) virion

  B) receptors

  C) endocytosis

  D) envelope

  E) Translocation

  F) plasma membrane

  G) Uncoating

  H) proteins

  I) mRNA

  J) release

  
• Double-stranded DNA viruses replicate in the nucleus of the cell. Viral DNA is transcribed by cellular DNA-dependent RNA polymerase (transcriptase) to form mRNA.
• Single-stranded DNA viruses replicate in the nucleus of cell and use cellular DNA polymerase to synthesise double-stranded DNA which is then transcribed by cellular DNA-dependent RNA polymerase (transcriptase) to form mRNA.
• Double-stranded RNA viruses have segmented genomes. Transcription occurs in the cytoplasm under direction of viral transcriptase and negative sense strands are used to transcribe mRNA molecules.
• Positive sense single stranded RNA viruses have genomes that can act directly as mRNA and bind to ribosomes to be translated to a single polyprotein. The polyprotein is cleaved to functional and structural proteins.
• Negative sense single stranded RNA viruses contain RNA-dependent RNA polymerase. The transcription of the positive sense mRNA uses genomic RNA as a template. The positive sense mRNA then acts as a template for negative sense viral genomes. Most replicate in the cytoplasm, some exceptions replicate in nucleus.
• Protein synthesis in DNA viruses:

  • Proteins sequentially transcribed and translated in order of need (temporal)
  • Early- proteins involved in replication and suppression of host
  • Late- structural proteins
• Protein synthesis in RNA Viruses:

  • Proteins produced concurrently, where structural and replication proteins are made at the same time.
• The site of protein synthesis depends on the type and function:

  • Membrane bound ribosomes create membrane proteins and glycoproteins
  • Free ribosomes create soluble proteins including enzymes
  • Most viral proteins undergo post-translational modification
• Assembly and release of virions in non-enveloped viruses:

  1. Structural proteins assemble spontaneously to form procapsids
  2. Viral nucleic acid incorporated into procapsid
  3. Proteolytic cleavage of specific procapsid polypeptides may be required
  4. Released following cellular disintegration
  5. Assembly in cytoplasm or nucleus
  6. Variable between different viruses
• Assembly and release of virions in enveloped viruses:

  1. Acquisition of envelope by budding cell membranes
  2. Some acquire from membrane of rough endoplasmic reticulum or golgi body rather than cell membrane
  3. Cell membrane modified prior by insertion of virus transmembrane glycoproteins
  4. Nucleocapsid binding to protein depends on morphology
• Bacteriophages are viruses that infect bacteria. Bacteriophages have a lytic or lysogenic replicative cycle.
• The disease induced depends on the tissues infected and damage caused and the immune response to viral replication may cause damage to tissues. Tissue repair/the regeneration capacity of tissue may determine long term impacts of infection.
• Multiple factors may influence the emergence of a virus. It's generally not new, but one of many existing viruses that mutated, disseminated and/or spread to a new host species.
• Emergence of a virus is facilitated by changes in host behaviour as well as environmental change, such as:

  • Growing world population
  • Increased use of animals to feed them
  • Human movement
  • Urbanization or Deforestation
  • Human behaviour and culture
  • Changes in host and vector ranges
  • E.g. chikungunya vector Aedes aegypti only, mutation A. albopictus
  • Climate change and vector geographical range
• Epidemic: rapid spread in human population in short time
• Epizootic: rapid spread in animal population in short time
• Pandemic: spread to several continents globally
• Outbreaks due to mutation are unusually high in RNA viruses as RNA polymerase does not proofread or correct errors in replicating genomes. Some mutations change existing viruses into new strains and can cause disease in individuals immune to the ancestral virus. Seasonal flu epidemics are caused by new strains.
• Outbreaks due to dissemination is a combination of social and environmental factors, for example: HIV / AIDS which went unnamed and unnoticed for decades. There are often repeated spill-over events. HIV emerged from chimps, driven by bushmeat hunting which accelerated due to the increased urbanization in Central Africa. The virus entered an expanding global air network and was accelerated further by changes in sexual behaviour, drug use, trade in blood derivatives, and population mobility.
• Zoonoses outbreaks occur when viruses spread from animals to humans. 75% of new human diseases have a zoonotic origin with increasing interdependence on animals and their products. Animals that transmit but are generally unaffected are a reservoir. Animals can be infected by more than one strain due to genetic recombination leading to new strains.
• Viral diseases of animals that are of particular concern to human health and/or of economic importance in animals are classified as notifiable diseases. This allows the government to implement control measures to prevent further disease spread.