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Flashcards in Viral Pathogens II Deck (13)
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Describe the typical course of the HIV-1 infection 

  • In a typical untreated, ten billion virions are made and destroyed every day during the chronic phase 
  • HIV is tropic for CD4+ T cells 
    • Throughout the course of infection 
      • You get fewer CD4+ T cells → this becomes undetectable after many years 
      • You get more RNA genome (as virus is replicating) 
  • The inexplorable depletion of CD4+ T cells during infection leads to AIDS (acquired immune deficiency syndrome) and mortality through opportunistic infections 



Define Viral load

a measure of the number of viral particles present in an organism or environment, especially the number of HIV viruses in the bloodstream


Why do retroviruses invade the human system? 

  • Viruses will try to evade the IR, some IR are recognised by specific cells in the immune system, these cells will recognise and kill cells infected by virus 
  • To evade this type of immune response some viruses will replicate in the immune cell whose function is to recognize and kill infected cells 
  • Replication in immune cells hides the virus from immune cells + inhibits cell function 
  • Inhibition of immune cell function will allow other pathogens to replicate in virus, infected host = disease occurs 


What are the two types of CD4+ T cells the virus can infect? 

  • NON-PERMISSIVE (95%) → Do not allow the virus to be replicated fully 
  • PERMISSIVE (5%) → Allow the virus to replicate

The virus is able to get into both cells and they have provoked states which are disadvantageous to the host cell 


Describe what happens with regards to viral infection in permissive and non-permissive CD4+ T-cells

  • Permissive CD4+ T cells 
    • dsDNA produced by virus is recognised as foreign 
    • Caspase 3 is activated = mediates apoptosis 
    • The virus is able to shut down this response 
      • Response is shut down due to viral accessory proteins/regulatory proteins such as Nef and Vif
  • Non-permissive CD4+ T cells 
    • No full replication of the virus 
    • The foreign NA is detected by IFI16 DNA sensor (activates IR) 
    • Caspase 1 activation and pyroptosis 
    • Pyroptosis = Cell death and excretion of immune factors (hence more inflammation 


Through what mechanism are CD4+ T cells lost in HIV? 

  1. Direct viral infection of permissive T-cells is not as important as the indirect effect through non-permissive T-cells 
  2. Pyroptosis and hence inflammation will recruit more healthy CD4+ T cells (+ feedback) 
  3. The inflammatory state will hypercharge the immune system which leads to more inflammation due to cell death and pro-inflammatory cytokine release and cellular contents 
  4. Neutrophils will come in and act on CD4 cells = more inflammation 
  5. Exhaust mechanism will exhaust the numner of CD4+ cells which are functional and present 
  6. Constant activation of immune system via infection (direct) and inflammation (indirect) = loss of CD4+ cells 


How is HIV linked to opportunistic infections? 

List some HIV-associated pathogens. 

  • Loss of T cells can cause an individual to become chronically immunodeficient = increased chance of opportunistic infection = mortality 
  • Most patients with HIV will not die from HIV but through opportunistic infections 


How do opportunisitc infections due to HIV/AIDS relate to cancer? 

  • Opportunistic infections can lead to cancer such as two viruses Herpes simplex and Kaposis sarcoma herpes virus 

Both viruses will infect via two routes 

  1. Primary infection 
  2. Reactivation from latency 

Primary infection can be resolved through immune supression, the infection can move to sites that the immune system cannot access. Here the virus can reside without replicating = LATENCY 

Reactivation from latency occurs upon immunodeficiency 


What is latency? 

When can reactivation from latency occur? 

Latency = infection is inactive or dormant it is not actively replicating and potentially causing symptoms


Immunodeficiency will result in reactivation upon latency 


Describe the activation of a disease from latency. 

Example = Herpes Simplex Virus 

  • Virus will enter the host cell, replicate and move into nerves of nervous system 
  • We dont have immune surveillance in NS as immune cells cant access blood brain barrier 
  • Virus will move up dendrites and to CNS 
  • Immune system will constantly be surveying you and sending messages to latent infections in CNS that the immune response is still here
  • When immunodeficiency occurs, there are no longer any signals so the virus will reactivate from latency and result in a worser infection 


Describe the viral oncogenesis of AIDS-Kaposi's Sarcoma 

  • Virus will get in and you get KS progenitor cells → becomes de novo/ primary infection 
  • De novo infection will lead to latent infection of cells of immune system (B cells) 
  • Virus will remain latently (isnt replicating or at a very low level) 
  • Some viral/ cellular cue occurs = viral reactivation 
  • T cell and B cells interaction is constant in healthy individual,  this interaction avoids reactivation from latency 
  • In HIV/AIDS sufferer no T cells so reactivation is permitted 
  • Allows reinfection of new cells 
  • Some B-cells may be permissive to oncogenic effects, we think that the B-cells themselves have cued to be permissive and allow cancer to form 


What are som ways in treating HIV and specifically KSHV? 

  • ART or Anti-viral therapy = Stops HIV replication and stops inflammation 
  • Gancyclovir ART = Direct acting anti-viral drug prevents replication of KSHV in B-cells and other cells 


List some viruses that can cause cancer

  • Human papilloma viruses (HPVs) – Papilloma virus, circular dsDNA genome, skin cancer
  • Epstein-Barr virus (EBV) – Herpes virus, linear dsDNA genome, lymphoma
  • Hepatitis B virus (HBV) – Hepadnavirus, circular dsDNA genome, carcinoma
  • Hepatitis C virus (HCV) – Flavivirus, ssRNA genome, carcinoma
  • Human herpes virus 8 (HHV-8) - Herpes virus, linear dsDNA genome, lymphoma
  • Human T-lymphotrophic virus-1 (HTLV-1) – Retrovirus, RNA-DNA genome, leukemia/ lymphoma
  • Merkel cell polyomavirus (MCV) – Polyomavirus, dsDNA genome, carcinoma

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