Viral Pathogens II Flashcards
Typical course of HIV-1 infection
- In a typical untreated patient, ten billion virions are made and destroyed every day during the chronic phase of disease I (year to year).
- There is an inexorable depletion of CD4 T cells during infection is what leads to immunodeficiency (AIDS) and mortality (via opportunistic infections).
- Over 6 weeks, there is a peak of the virus replication and a significant decrease in T cells.
- Over years, the virus does not kill the individual immediately, instead the number of T cells get fewer and fewer.
- Until around 19 years with the infection, when there is almost undetectable T cell count and very high HIV RNA levels in the body. ]
When do symptoms arise in HIV?
Symptoms occur due to lack of T cells occur, these include fatigue and organ failure.
What is the bimodal effect of HIV?
If the HIV kills the host very quickly, it will no longer be able to replicate itself and therefore by doing it over years it can replicate itself.
How do viruses evade the immune responses?
- Some viruses replicate in the immune cells whose function is to recognise and kill infected cells.
- Doing this hides the virus from the immune cells and inhibits immune cell function.
- Inhibition of immune cell function allows other pathogens to replicate in virus infected hosts and therefore causes diseases.
- Therefore, killing the CD4 T cells is good because it means there are no longer anymore cells that will recognise the virus and kill it.
What are the two types of T cells?
Non-permissive and Permissive
Non-permissive T cells
- Cells in which the virus isn’t able to replicate.
- 95% of cells
- This means in most CD4 T cells the virus encounters, they are not able to replicate.
- The virus enters the cell but isn’t able to replicate, therefore you don’t get full viral dsDNA but you will still get some foreign viral nucleic acids in the cell.
How does the cell detect the foreign viral nucleic acids in them?
- Detected by the IFI16 DNA sensor.
- Via a number of mechanisms, the IFI16 molecule is able to activate a number of immune responses including innate, antiviral and inflammasome response.
- These responses allow the cell to make immune-proteins and inflammatory molecules.
What is pyroptosis?
A highly inflammatory form of programmed cell death that occurs most frequently upon infection.
Also get the excretion of the immune molecules made which travel in the lymphoid tissue to inform other cells that there is an infection.
What is a mediator for pyroptosis?
Active caspase 1
Permissive T-cells
- 5% of CD4 T cells
- Cells in which the virus can fully replicate
- The virus enters the cell, carried out reverse transcriptase and so in the cell there is now ds viral DNA.
What happens when the dsDNA enters the nucleus in the T cells?
It is recognised as foreign and triggers the Caspase 3 which is the mediator for apoptosis. However, the virus has mechanism to shut this down.
What is the function of VIF?
A specific protein which is involved in evading the immune response to virus replication.
What is permissive cell death?
The virus is not efficient in the evading process so there is permissive cell death.
Describe the direct effect of HIV on the cells (step one of whole cycle)
- HIV infects the cell.
- HIV leads for the CD4 T cells to carry out pyroptosis.
- The release of cytokines and other pro-inflammatory mediators causes inflammation. This acts as a warning signal to tell other cells that there is an infection.
- Inflammation causes the migration and recruitment of more healthy CD4 T cells. This is good for HIV as there are more cells to infect and replicate. This is also a positive feedback mechanism and step 1 happens again.
Describe the indirect effect of HIV on the cells (step two)
- The inflammation that recruits the CD4+ cells also hypercharges the immune system, so you get migrations of cells such as neutrophils and monocytes to the infected area.
- The neutrophils act on the CD4 T cells causing more inflammation. This leads to the cycle ending in step 3 with more inflammation.
What leads to the depletion of CD4 T cells over time?
The exhaustion (charging) of the immune system which leads to the depletion of the CD4 T cells which are functional and present over time. This is why people with HIV patients are likely to get opportiunistic infections via HIV associated pathogens because they’re very chronically immune-deficient.
Viruses that are HIV associated pathogens
Herpes Simplex virus (HSV)
Kaposi’s sarcoma herpesvirus (KSHV)
Bacteria that are HIV associated pathogen
Mycobacterium Tuberculosis
Salmonella
Fungus that are HIV associated pathogen
Candida
Cryptococcus neoformans
Parasites that are HIV associated pathogen
Cryptosporidium
Toxoplasma gondii
What is AIDS?
Potentially life-threatening infections and illnesses that happen when the immune system has been severely damaged by HIV. For example, cancers and opportunistic infections: Kaposi’s sarcoma and Herpes simplex virus - oral, genital and anal.
What are the possible routes of infection?
Primary and Reactivation from latency
Primary infection
The body gets exposed to a pathogen for the first time and the pathogen colonises the body. It can be resolved by immune suppression.
Reactivation from latency
When the virus gets in and either replicates very slowly or doesn’t replicate at all. The idea is that the virus hides from hte immune system, by moving to sites in the host that the immune system does not access such as the nervous system. Reaction from latency occurs upon immunodeficiency.
Describe the mechanisms of latency and immune-deficiency
- The HIV will start by infecting the epithelial cell where it will replicate.
- It will then enter the nervous system, which is good for the virus as there is no immunosurveillance due to most of the immune cells not being able to cross the blood brain barrier.
- HIV enters and reaches the dendrites and the CNS. This is why HIV can go from vaginal or anal transmission to the brain. The virus can rest in the neurons waiting for immunodeficiency (hiding from the immune system which is latent).
- When there is immunodeficiency, the virus is reactivated from the latent stage.
- If the virus replicates in the dendrites, there will be a serious CNS disease and mortality.
How does the virus detect if the body is immunodeficient?
It will detect by going back to the site of infection to see if the level of T cells decreased or not. It has then the virus will start replicating and infecting again.
Describe the disease and interaction of HIV with the immune system
- On the right side, the virus infects the cells (K5 progenitors) and de non-novo infections occurs (primary infection). This then leads to latent infection of cells in the immune system (B cells).
Name viruses that cause cancer
- Human papilloma viruses (HPVs)
- Epstein Barr virus (EBV)
- Hepatitis B virus (HBV)
- Hepatitis C virus (HCV)
- Human herpes virus 8 (HHV-8)
- Human T lymphotropic virus (HTLV-1)
- Merkel cell polyomavirus (MCV)
