Viral Pathogenes; Classification, Biology, Diseases II

Question 1

How does a typical untreated HIV patient deal with the infection?

Answer 1

In a typical untreated patient, ten billion virions are made and destroyed every day during the chronic phase of disease

Question 2

Describe the relationship between T cells and viral RNA as infection progresses

Answer 2

As infection continues CD4 T cells decrease but viral RNA increases

Question 3

What causes immunodeficiency in HIV Infection?

Answer 3

The inexorable depletion of CD4 T cells during infection ultimately leads to immunodeficiency (AIDS) and mortality (via opportunistic infections)

Question 4

How does the immune response hinder HIV infection?

Answer 4

Viruses must evade immune responses; mediated by specific cells that recognize and kill virally infected cells

Question 5

How do viruses evade the immune response?

Answer 5

Some viruses replicate in the immune cells whose function is to recognize and kill infected cells

Question 6

How does replicating in immune cells evade the immune response?

Answer 6

Replication in immune cells hides the virus from immune cells and inhibits immune cell function

Question 7

What is the consequence of immune cell function inhibition?

Answer 7

Inhibition of immune cell function allows other pathogens to replicate in virus infected hosts
> Opportunistic infections of HIV associated pathogens

Question 8

What are the 2 types of advantageous T cells to HIV?

Answer 8

• Non-permissive CD4 T-cell; cannot replicate fully

- Permissive CD4 T-cell; virus can replicate

Question 9

How does HIV replication differ among different T cells?

Answer 9

HIV can get into both kinds of T cells but will replicate properly only in permissive T-cells

Both types have disadvantageous components to HIV

Question 10

Outline the disadvantage to HIV of replicating in CD4 T cells?

Answer 10

The nucleus is a tightly regulated organelle; any foreign DNA is recognised and there are mechanisms in order to remove it via apoptosis due to caspase 3 activation - immune response

Question 11

How do permissive T cells overcome the disadvantageous immune response to HIV?

Answer 11

In the permissive cell, HIV polyproteins (Vyf, Nyf, VPR) can deactivate apoptosis activation - doesn’t always occur

Question 12

Outline how the immune response against HIV can be deleterious towards other healthy cells

Answer 12

1. HIV infection
2. Apoptosis causes cell death
3. Release of proinflammatory cytokines and cellular
   contents
4. Inflammation; recruits more CD4 T-cells
5. Positive feedback mechanism; more CD4 T cells =
   more HIV infection

Question 13

How does HIV infection cause immunodeficiency?

Answer 13

Inflammatory immune response hyper charges the immune system causing neutrophil & monocyte migration to unaffected cells ⇒ increased inflammation and exhaustion of immune response - immunodeficiency

Question 14

What are the viral HIV associated pathogens?

Answer 14

• Herpes simplex virus (HSV)

- Kaposi’s sarcoma herpesvirus (KSHV)

Question 15

Name the fungi HIV associated pathogens?

Answer 15

• Candida

- Cryptococcus neoformans

Question 16

Give examples of the parasite HIV associated pathogens

Answer 16

• Cryptosporidium

- Toxoplasma gondii

Question 17

What are the bacterial HIV associated pathogens?

Answer 17

• Mycobacterium tuberculosis

- Salmonella

Question 18

What condition is a result of unchecked HIV?

Answer 18

Large number of unchecked HIV infections (e.g. KSHV; kaposi sarcoma herpes virus) colonises and infect its host

Question 19

What is the consequence of KSHV?

Answer 19

Sarcoma lesions unchecked can lead to metastatic sarcoma disease; systemic infection → neuronal damage - painful and rapid mortality

Question 20

What are the 2 methods of viral associated HIV Pathogen infections?

Answer 20

Two possible routes of infection

1. primary infection
2. reactivation from latency

Question 21

How does primary infection become latent?

Answer 21

Primary infection resolved (typically by immune suppression) and infection moves to sites in host that immune system doesn’t access
In these sites the virus resides without replicating: latency

Question 22

What causes KSHV reactivation from latency?

Answer 22

Reactivation from latency occurs upon immunodeficiency

Question 23

Outline how KSHV infection is reactivated form latency

Answer 23

1. HSV exposure through skin; epithelial cell infection
2. Viral replication in host cell and then moves into nervous system
3. Moves into dendrites and CNS
4. Immune regulation sends signals to latent infections
5. When immune signal is no longer present (immunodeficiency), virus reactivates from latency and travels back to site of infection ⇒ productive infection

Question 24

Where does productive infection occur (reactivated from latency)?

Answer 24

Productive infection can occur in the cell of infection origin or neighbouring cells

Question 25

Where do latent infections commonly reside?

Answer 25

Nervous system as it has poor immune regulation due to the fact immune cells don’t cross Blood brain barrier

Question 26

Why does KSHV infection not reactivate from latency before immune deficiency?

Answer 26

As KSHV infects B cells it interferes with B cell - T cell interactions that would normally occur

Due to lack of interaction between immune cells there is no impotence for virus to reactivate from latency

Question 27

What mechanism induces reactivation of KSHV from latency

Answer 27

In HIV sufferers, there is a lack of T cells ∴ a lack of immune signals indicating no B-T cell interaction

This causes reactivation to occur

Question 28

Outline how reactivation of KSHV can lead to cancer

Answer 28

1. Virus is replicating at a very low level / not at all
2. Cellular/viral cue occurs; inflammatory cytokines
3. Reactivation from latency
4. Lytic, productive, cytopathic, immunogenic effects
   occur from virus production
5. Reinfection of new cells
6. Some B cells become oncogenic - uncontrolled cell
   division

Question 29

Why does KSHV not develop into cancer in all infection cases?

Answer 29

KSHV only occurs in very specific (cancer) circumstances;

• Just like HIV some B cells are permissive / non-permissive
• Thought that B cell morphology is altered to allow cancer to form

Question 30

How do lesions induce production of oncogenic cells in KSHV?

Answer 30

KS lesions cause a positive feedback mechanism as more B cells undergo transformation into oncogenic cells

Question 31

How is KSHV treated?

Answer 31

• ART (antiretroviral therapy) stops HIV infection and inflammatory response
• Ganciclovir direct acting antiviral drug prevents replication of KSHV in B cells