Viral Pathogenes: Classification, Biology, Diseases - II Flashcards
Describe the typical course of an HIV-1 infection.
In a typical untreated patient, ten billion virions are made and destroyed every day during the chronic phase of disease.
CD4+ T cells are key for the response of the immune system.
As the course of the infection goes on:
- You get fewer CD4+ T cells – this becomes undetectable after many years.
- You get more RNA genome (this means that the virus is replicating).
Viral replication is chronic and this means there is more of an opportunity for it to infect others.
The inexorable depletion of CD4+ T cells during infection ultimately leads to immunodeficiency (AIDS) and mortality (via opportunistic infections).
Why do retroviruses invade the immune system?
Viruses must evade immune responses. Some immune responses are mediated by specific cells of the immune system. These immune cells recognize and kill cells infected by virus.
To evade this type of immune response, some viruses replicate in the immune cells whose function is to recognize and kill infected cells.
Replication in immune cells hides the virus from immune cells and inhibits immune cell function.
Inhibition of immune cell function allows other pathogens to replicate in virus infected hosts and, thus, disease occurs.
What are the two types of CD4+ T-cells with regards to viral infection?
There are non-permissive CD4 T-cells, which make up 95%, and permissive CD4 T-cells, which make up 5%.
The virus can get into both cells, and they both have provoked states that are disadvantageous to the host cell.
Describe what happens with regards to viral infection in the permissive and non-permissive CD4 T-cell.
In the PERMISSIVE:
- the dsDNA is recognised as foreign
- caspase 3 is activated, which mediates apoptosis
- the virus is able to shut down this response
In the NON-PERMISSIVE;
- there is no full replication of the virus
- the foreign nucleic acid is detected (by IFI16) - this activates the immune response
- you then get pyroptosis - cell death, but during you get the secretion of the cell’s immune factors
How does immune response aid the virus?
The direct effect of viral infection on T-cells is not as important as the indirect effect.
Inflammation brings more healthy CD4 T-cells to the virus– this is a positive feedback mechanism that allows virus to infect more healthy T-cells.
Inflammatory state hypercharges the immune system, which again leads to more inflammation due to the cell death and the release o pro-inflammatory cytokines and cellular contents.
The neutrophils come in and act on the CD4 cells and that causes even more inflammation.
The exhaust mechanism exhausts the number of CD4 cells that are functional and present over time.
Constant activation of the immune system via the direct effects of infection and indirect effects of inflammation lead to the loss of the CD4 T-cells.
List some HIV-associated pathogens.
VIRUS:
- Herpes simplex virus (HSV)
- Kaposi’s sarcoma herpesvirus (KSHV)
BACTERIA:
- Mycobacterium tuberculosis
- Salmonella
FUNGUS:
- Candida
- Cryptococcus neoformans
PARASITE:
- Cryptosporidium
- Toxoplasma gondii
How do opportunistic infections due to HIV/AIDS relate to cancer?
The opportunistic infections can sometimes lead to cancer. The two viruses Herpes Simplex and Herpes Virus 8 are directly involved in cancer.
There are two possible routes of infection:
(i) primary infection
(ii) reactivation from latency
Primary infection can be resolved (typically by immune suppression) and infection moves to sites in the host that the immune system does not access. In these sites the virus resides without replicating: latency.
Reactivation from latency occurs upon immunodeficiency.
Describe the activation of a disease from latency with the example of the Herpes Simplex Virus.
The virus enters the host cell, replicates and then moves into the nerves of the nervous system.
We don’t really have immune surveillance in the nervous system as a lot of the immune cells don’t access the blood brain barrier.
The virus can then move up the dendrites and up to the CNS (even by genital transmission of virus).
The immune system is constantly surveying you and sending constant messages to latent infectious viruses up your CNS that your immune system is still there.
When you take this away (i.e. immunodeficiency) , the virus reactivates from latency and travels all the way down to the site of infection and you get productive infection again – either from the cell it came from or from other cells that are there.
Describe the viral oncogenesis of AIDS-Kaposi’s sarcoma.
The virus gets in and you get KS progenitor cells – this become the de novo infection.
De novo infection leads to latent infection of cells of the immune system (in this case B cells).
The virus gets into B cells (and then the immune system cannot get into it).
The virus then sits there latently. Latent replication: isn’t replicating or replicating at a very low level.
Some particular viral or cellular cue occurs, which then reactivates the virus.
The interactions between T-cells and B-cells are constant in the immune system – without this, there is no way the virus can reactivate from latency.
If this is a HIV sufferer, the T-cells signal is gone and then this allows some form of reactivation signal from the virus.
It proceeds to follows the lytic pathway, and since it’s a positive feedback scheme, you see the reinfection of new cells. There are also some B-cells that are permissive to oncogenic effects and some that are not – we think some of the B-cells themselves have to be cued to be permissive and allow the cancer to form.
Describe the asymptomatic KSHV (Kaposi’s Sarcoma Herpes Virus) infection in a healthy individual.
The primary infection moves to a latent infection (i.e. things that are not transformed).
There is a cue that allows for reactivation (e.g. inflammatory cytokines).
We then get lytic production – and then, we don’t understand how, but some of these cells then become oncogenic (uncontrolled replication).
There is positive feedback and uncontrolled replication of these particular B-cells.
There is also an inflammatory response whilst there is oncogenesis.
KS lesions are cells that are replicating again and again, and you see the production of these inflammatory molecules – these produce more inflammatory stimuli, which forms more latent transformed cells.
There are certain ways to combat this:
- ART or Anti-viral therapy – stops HIV replication and stops the inflammation
- Gancyclovir ART – direct-acting anti-viral drug that which prevents replication of KSHV within Bcells 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
