Week 8 Viral Pathogenesis and Respiratory Viruses

• Viral pathogenesis


  It is the process by which viruses cause disease. This encompasses the entire infection cycle, from entry to transmission, and the effects on both individual cells and the host organism.
• Key requirements for successful viral infection

  • Sufficient virus must be available to initiate infection
  • Cells at the site of infection must be accessible, susceptible, and permissive for the virus
  • Local host anti-viral defense systems must be absent or initially ineffective
• Viruses can enter their host via different entry portals including the skin, respiratory tract, gastrointestinal tract, genitourinary tract, and conjunctiva.
• Virus shedding and transmission can occur via horizontal transmission from host to host and vertical transmission from host to progeny.
• Virulence


  "capacity" to produce disease
• Tropism

  • what cells within the host does the virus infect
  • effected by cell receptors, route of infection, intracellular molecular restrictions
• Fomite


  an inanimate object that is capable of transmitting infectious organisms from one individual to another
• Vector borne / Arboviral disease


  Viral diseases spread to people by an infected mosquito, tick, etc. (The insects act as vectors)
• Viral Pathogenesis loosely categorized by:

  • Routes of entry
  • Localization and spread
  • Shedding of virus and transmission
• Routes of entry

  • skin (blood borne pathogens)
  • respiratory tract
  • gastrointestinal tract
  • genitourinary tract
  • conjunctiva
• Localized Spread

  many viruses multiply in epithelial cells at site of entry -->

  produce a spreading infection -->

  then shed directly to exterior

  Surface Infection - failure to spread to deeper tissues
• Systemic Spread

  • polarized infection of epithelial cells and spread
  • Targeting of viral budding to apical or basal surfaces of polarized cells may define subsequent spread
  • Systemic spread is usually via blood (HIV, measles) or the nervous system (HSV)
• Horizontal Transmission


  Infection from host to another host of the same generation
• Direct (Horizontal)


  Host-to-host by contact thru:

  • •skin lesions – papillomavirus
  • saliva – rabies, mumps, CMV, EBV, HBV
  • mechanical trauma – HIV, HSV
  • or aerosols, eg influenza, measles, rhinoviruses
• Indirect (Horizontal)


  Host to fomites to host

  • Fomites: food, water, needles, vector-mediated
  • eg, hepatitis A, norovirus, hepatitis B/C, HIV, Dengue virus
• Vertical Transmission


  From Host to Progeny
• Transplacental [Congenital] (Vertical)


  Cytomegalovirus (CMV), parvovirus B19 cross the placenta and can cause fetal infections, as can zika virus

  
• Intrapartum (Vertical)


  Infection with HIV or HBV can occur during birth (during passage of infant through birth canal)
• [1] Acute Infection

  Rapid and self-limiting

  In-apparent acute infections: successful infection, no symptoms, but viral spread

  Serious epidemics affecting millions/year (influenza, measles)

  Difficult problems – by the time you feel ill, the infection may be over and has spread!

  
• [2] Persistent Infection

  Long term, life of host

  
• [3] Most persistent infections begin as acute infections

  
• Persistent CHRONIC Infection

  • No single mechanism
  • Slow progressing infection, often noncytopathic (HBV and HCV), and often results in death if untreated (HCV, HBV, HIV)

  
• Persistent LATENT Infection

  • Usually an initial acute phase, followed by viral relocation to cells enabling latency.
  • HSV and VZV viruses establish latency in ganglion by shutting down their replication cycle to avoid host immune detection.
  • HIV is able to establish some form of latency in cells with slow turn-over (ie resting memory T cells)

  
• Factors that effect viral pathogenesis outcomes

  • Genetic - defects in the immune system genes can effect the outcome of viral infections
  • Age - persons over 50 years old are much more likely to develop severe symptoms
  • Previous exposure to the pathogen - Protective immunity
  • Health status - immunosupression/ malnutrition or pregnancy/ co-morbidities ;HSV/Measles - malnutrition; More pathogenic in immunocompromised; Pregnancy- zika virus; Co-mobidities – HBV and HCV co-infection
  • Chance - Its often a close race: Immune response Vs pathogen
• Virulence can be quantitated

  In vivo

  • Mean time till death
  • Mean time to appearance of symptoms
  • Measurement of symptoms: fever, weight loss
  • Measurement of clinical pathology: lesion number (poliovirus); reduction in blood CD4+ lymphocytes (HIV-1)
  • Measurement of viral load
• Virulence can be quantitated


  In vitro

  • Viral load
  • Cell death
• Viral virulence genes can be placed in one of three main general classes.

  1. Gene products that alter the ability of the virus to replicate.
  2. Gene products that modify the host’s defense mechanisms.
  3. Toxic viral proteins