Classification, Biology and Disease II

Question 1

Describe the typical course of HIV-1 infection?

Answer 1

The number of T cells goes down during primary infection whereas the viral load, the number of HIV viral RNA genomes per ml of blood, goes up
This resolves itself in an odd way which leads to the HIV copies falling towards a viral load set point, the minimum number of HIV particles you can have without the immune system detecting it but still being able to replicate
However the T cell numbers gradually falls
That modest fall over time is called clinical latency where the person doesn’t see the onset of symptoms
After the onset of symptoms there is a further drop in T cells which somehow stimulates more HIV copies to be produced
The number of T cells drops to the point where opportunistic infections overwhelm the individual and then death typically occurs
In a typical untreated patient, ten billion virions are made and destroyed every day during the chronic phase of disease
The inexorable depletion of CD4 T cells during infection ultimately leads to immunodeficiency (AIDS) and mortality (via opportunistic infections)

Question 2

Why do some viruses replicate in immune cells?

Answer 2

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.

Question 3

How could HIV promote T cell killing directly and indirectly?

Answer 3

Directly by infecting the T cells
However not all T cells are permissive to HIV infection, 95% are not permissive
Permissive T cells which have CD4 on their cells surface which allows the virus to replicate
The production of new viruses during permissive infection activates the cellular process of apoptosis
In non-permissive T cells CD4 is still on the surface which allows the virus to get in but doesn’t allow the virus to replicate
It allows the virus in, which is recognised by the innate immune system and that activates the cell killing mechanism of pyroptosis

Question 4

What happens to immune cells when pyroptosis occurs?

Answer 4

Pyroptosis causes inflammation
Inflammation means you’ll get recruitment of more T cells to the site of infection where they themselves can be infected etc.
Inflammation itself can cause cell death in uninfected cells
So you have this positive feedback of infection

Question 5

What is meant by opportunistic infections?

Answer 5

Inhibition of immune cell function allows other pathogens to replicate in virus infected hosts and, thus, disease occurs: Opportunistic infections of HIV associated pathogens.

Question 6

What are some HIV-associated pathogens?

Answer 6

Virus
	- Herpes simplex virus (HSV)
	- Kaposi's sarcoma herpesvirus (KSHV)
Bacteria
	- Mycobacterium tuberculosis  
	- Salmonella
Fungus
	- Candida
	- Cryptococcus neoformans
Parasite  
	- Cryptosporidium  
	- Toxoplasma gondii
The major cause of fatalities are the viral pathogens

Question 7

What are the two possible routes of infection in HIV-affected individuals?

Answer 7

Two possible routes of infection in HIV affected individuals
(i) primary infection
- You have an HIV infected individual who does not have either virus and then get them
(ii) reactivation from latency
- When the person already has HIV associated pathogens but it reactivates due to the depletion of T cells due to HIV infection
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

Question 8

How does the Herpes simplex virus become latent?

Answer 8

The epithelial cell which the virus encounters and replicates into the nerve cells or dendrite whose processes are connected to the epithelial cell
The virus can move up and down axons from PNS and CNS
If the virus just sits in the dendrites axons or cell body it isn’t replicating and the immune system cannot detect it.
When you lose T cells, the virus comes out and back into epithelial cells to replicate again

Question 9

What are some viruses that cause cancer?

Answer 9

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