Viral pathogens: classification, biology, disease 1

Question 1

What happens once viral particles get out of the cell in HIV? What cells do they want to infect?

Answer 1

→ Once viral particles get out of the cell, they want to infect other cells.
→ HIV wants to infect T cells because T cells have a CD4 molecule on their surface (which is a receptor for HIV-1).
→ So HIV recognises the CD4 receptor so enters T cells and begins to replicate.
→ This replication causes killing of T cells

Question 2

Describe a typical course of HIV-1 infection

Answer 2

→ The number of T cells goes down during primary infection while the number of HIV replicates goes up.
→ So more HIV= more T cell killing.
→ The number of HIV copies falls to a viral load set point- (minimum number of HIV particles you can have without the immune system detecting it but the virus is still replicating)
→ But during the period of ‘clinical latency’, the number of T cells gradually decreases (clinical latency- no obvious symptoms of the fall in T cells)

→ Only see an onset of symptoms years later ( about 7 years after primary infection)

→ Then around 10 years later, T cell numbers drop so low, opportunistic infections overwhelm and leads to death.

→ 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 3

Why is immunodeficiency advantageous to the virus?

Answer 3

→ 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: Opportunistic infections of HIV associated pathogens.

Question 4

What is the difference in cell death in non-permissive and permissive CD4 T-cells?

Answer 4

→ Non permissive CD4 T-cells allow the virus in. → The virus is recognised by the innate immune system and that activates the cell killing mechanism.
→ Leads to cell death by PYROPTOSIS.

Cell death by APOPTOSIS in permissive CD4 T-cells

Question 5

What does Pyroptosis cause?

Answer 5

→ Pyroptosis causes inflammation which means you would get more recruitment of T cells to site of entry.
→ Positive feedback loop created- infection causes more recruitment of T cells which leads to more infection

Inflammation itself can cause T cell killing

Question 6

Give examples of HIV associated pathogens

Answer 6

Virus: (most commonly cause death)
Herpes simplex virus (HSV)
Kaposi’s sarcoma herpesvirus (KSHV)

Bacteria:
Mycobacterium tuberculosis
Salmonella

Fungus:
Candida
Cryptococcus neoformans

Parasite:
Cryptosporidium
Toxoplasmagondii

Can only infect humans who don’t have a fully functional immune system (that’s why its the opportunistic infections of HIV)

Question 7

In HIV affected individuals, what are the 2 possible routes?

Answer 7

Two possible routes of infection:
(i) primary 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.

(ii) reactivation from latency (carrying a virus already and the depletion of T cells allows the virus to further colonise)

In these sites the virus resides without replicating: latency
Reactivation from latency occurs upon immunodeficiency

Question 8

What are some examples of viruses that cause cancer?

Answer 8

Human papilloma viruses (HPVs)
1. Papilloma virus
2. Circular dsDNAgenome
3. Skin cancer

Epstein-Barr virus (EBV)
1. Herpes virus
2. Linear dsDNAgenome
3. Lymphoma

Hepatitis B virus (HBV)
1. Hepadnavirus
2. Circular dsDNAgenome
3. Carcinoma

Hepatitis C virus (HCV)
1. Flavivirus
2. ssRNAgenome
3. Carcinoma

Human herpes virus 8 (HHV-8)
1. Herpes virus
2. Linear dsDNAgenome
3. Lymphoma

Human T-lymphotrophicvirus-1 (HTLV-1)
1. Retrovirus
2. RNA-DNA genome
3. Leukemia/ lymphoma

Merkel cell polyomavirus(MCV)
1. Polyomavirus
2. dsDNAgenome
3. Carcinoma