microbiology lecture 11 general virology

• Viruses are the smallest infectious agents
• Viruses are obligatory intracellular parasites because they have no metabolic activity
• Viruses can infect


  • Bacteriophages (bacterial viruses)
  • Animal viruses (infect vertebrates, including man)

  
• Viruses


  • Very small in size, ranging from 20-300 nm
  • Can be seen only under the electron microscope (except poxviruses)
  • Can pass through bacterial filters
  • Need ultracentrifugation for sedimentation

  
• Viruses


  • Obligatory intracellular parasites (can only replicate inside living cells)
  • Cannot be cultivated in the laboratory on artificial culture media (can only grow inside living cells)
  • Contain only one type of nucleic acid (DNA or RNA), never both
  • Not susceptible to antibacterial agents

  
• Viral cultivation methods


  • Cell culture (tissue culture)
  • Embryonated egg
  • Laboratory animals
• Virion


  The complete virus particle composed of a nucleic acid core (DNA or RNA) surrounded by a protein coat (capsid)

  
• Nucleocapsid


  The nucleic acid and the protein coat
• Enveloped viruses


  Have an additional lipoprotein layer called viral envelope
• Non-enveloped (naked) viruses


  Do not have a viral envelope
• Viral capsid


  • Formed of protein subunits called capsomeres
  • Protects the viral nucleic acid
  • Mediates attachment to host cell (in non-enveloped viruses)
  • Is the antigenic part of the virus
  • Is responsible for the viral symmetry

  
• Viral symmetry


  • Icosahedral (cubical) symmetry
  • Helical symmetry
  • Complex symmetry
• Viral nucleic acid (genome)


  Carries the genetic information of the virus and is responsible for virulence

  
• Most DNA viruses are double-stranded (ds) while most RNA viruses are single-stranded (ss)
• Positive-sense ssRNA


  Can be read directly by the host cell ribosomes
• Negative-sense ssRNA


  Cannot be read directly by the host cell ribosomes
• Viral envelope


  • Formed of lipoproteins and composed of lipids (derived from the host cell membrane) and glycoprotein spikes (of viral origin)
  • Enveloped viruses are less stable than naked viruses and are sensitive to heat, drying, detergents & lipid solvents
• Classification of viruses


  • By symptomatology (based on diseases they produce)
  • Hierarchical classification (into viral families, subfamilies, genera, species, types, subtypes & strains)
  • Baltimore classification (based on virus genome replication strategy)

  
• Except for the poxviruses, DNA viruses replicate in the nucleus of the host cell
• Except for the orthomyxoviruses (influenza viruses) & retroviruses (e.g., HIV), RNA viruses replicate in the cytoplasm of the host cell

  
• Viral replication cycle


  1. Attachment (adsorption)

  2. Penetration

  3. Uncoating

  4. Eclipse

  5. Synthesis of new viral components

  6. Assembly

  7. Release
• Attachment (adsorption)


  Adsorption of the virus to specific receptor sites on the surface of the susceptible host cell
• Penetration


  Occurs by endocytosis in case of non-enveloped viruses or by fusion of viral envelope with host cell membrane in case of enveloped viruses
• Uncoating


  The nucleic acid is released from the capsid by lysosomal enzymes and becomes available for replication
• Eclipse


  The time from uncoating until assembly of mature viruses, during which no infectious viruses can be detected in the host cell
• Synthesis of new viral components

  DNA viruses: mRNA is produced by the host's transcriptase

  RNA viruses: dsRNA - negative sense strand is transcribed by viral RNA polymerase (RdRp) into mRNA

  Positive strand (+ssRNA) - acts directly as mRNA

  Negative strand (-ssRNA) - positive RNA strand (mRNA) is produced by viral RdRp

  Retroviruses: complementary ssDNA (cDNA) is produced by reverse transcriptase, then integrated in host cell genome or transcribed to mRNA by host's DdRp
• Assembly


  The viral nucleic acids are enclosed within protein coats to form mature viruses (virions), either in the nucleus of host cell or in the cytoplasm

  
• Release


  New viruses are released either by lysis of the host cell (non-enveloped viruses) or by budding through the cell membrane (enveloped viruses)
• Entry routes of viruses


  • Inoculation (via the skin or mucosa)
  • Inhalation (via the respiratory tract)
  • Ingestion (via the gastrointestinal tract)
  • Sexual transmission (via the genitourinary tract)
  • Vertical transmission (mother-to-fetus or mother-to-baby)
  • Animal bite
  • Insect bite
• Primary viremia


  First entry of virus into the bloodstream, which is the route by which viruses get to their sites of infection
• Stages of virus replication


  1. Entry of viruses

  2. Attachment

  3. Penetration

  4. Uncoating

  5. Replication

  6. Assembly

  7. Release
• Entry of viruses


  Viruses gain entry into the host by: Inoculation, Inhalation, Ingestion, Sexual transmission, Vertical transmission, Animal bite, Insect bite
• Primary viremia


  First entry of virus into the bloodstream, route by which viruses get to their sites of infection
• Secondary viremia


  Shedding of virus from the infected organ, can cause infection at another site of the body
• Localized infections


  Common cold (rhinovirus), site of pathology is at the portal of entry, incubation period is relatively short, viraemia is absent, duration of immunity is usually short, antibodies involved are secretory IgA

  
• Systemic (deep) infections


  Measles (measles virus), site of pathology is at distant sites, incubation period is relatively long, viraemia is mostly present, duration of immunity is usually life-long, antibodies involved are IgM & IgG
• Host determinants of viral infection


  • Immune status
  • Genetic factors
  • Age
  • Hormonal factors
  • Nutritional status
• Fate of viral infections


  • Inapparent/subclinical/abortive infections
  • Apparent infections (acute disease)
  • Chronic viral infections
  • Latent viral infections
  • Slow infections
  • Oncogenic viral infections
• Latent viral infections


  The virus persists in a dormant form & may flare up intermittently to produce disease
• Chronic viral infections


  The virus is continuously detected with mild or no clinical symptoms