4- Viral pathogens: classification, biology, diseases - II

Question 1

How is the viral load determined?

Answer 1

➝ RT-PCR

Question 2

What leads to AIDS?

Answer 2

➝ inexorable depletion of CD4 cells

Question 3

What has HIV been adapted to do?

Answer 3

➝ give a very long period of infection

Question 4

What is the viral load set point?

Answer 4

minimum number of HIV particles you can have without the immune system detecting it but the virus still replicating

Question 5

How do HIV+ people die?

Answer 5

➝opportunistic infections

Question 6

What must viruses do to survive?

Answer 6

➝ evade immune responses

Question 7

How do viruses avoid being killed by immune cells?

Answer 7

➝ they replicate inside the immune cells whose function is to recognise and kill infected cells

Question 8

What is the advantage for a virus to replicate inside immune cells?

Answer 8

➝ hides virus from immune cells

➝ inhibits immune cell function

Question 9

What does inhibition of immune cell function allow?

Answer 9

➝ allows other pathogens to replicate in the virus infected hosts
➝ so disease occurs

Question 10

What are permissive T cells?

Answer 10

➝ have CD4 on cell surface

➝T cells in which the virus can replicate

Question 11

What % of T cells are permissive and non-permissive?

Answer 11

➝ 95% non-permissive

➝ 5% permissive

Question 12

Describe what happens when HIV enters a non-permissive CD4 cell?

Answer 12

➝ the virus enters but doesn’t replicate
➝ accumulation of incomplete reverse transcripts
➝ detection by IFI16 DNA sensor
➝ IFI16 activates the innate antiviral and inflammatory responses
➝ IFI16 inflammasome assembly
➝ Inflammasome response which activates caspase-1 and pyroptosis occurs
➝ cell death and excretion of all the inflammatory factors
➝ this warns other cells that there is some type of infection

Question 13

What happens in a permissive CD4 T-cell?

Answer 13

➝ the virus enters the cell and replicates
➝ processive reverse transcription
➝ Evading host detection
➝ double stranded DNA
➝ infection of CD4 T cell
➝ Activates caspase-2 
➝apoptosis occurs

Question 14

What three viral proteins are involved in evading the immune response to virus replication?

Answer 14

➝ VPR
➝ VIF
➝ NEF

Question 15

In permissive cells what is activated when there is foreign DNA in the cell?

Answer 15

➝ caspase-3 is activated which is a mediator of apoptosis

Question 16

Describe how the cycle of immune exhaustion occurs?

Answer 16

1) HIV infection
2) CD4 T cell death via pyroptosis and the release of pro-inflammatory cytokines and cellular contents occur
3) Inflammation occurs which is good for the virus because it brings more healthy CD4 cells that allows the virus to infect new cells- recruitment of health CD4T cells
4) the inflammatory state hyper charges the immune system so much that there is migration of the immune neutrophils and monocytes into the infected area
5) more inflammation occurs and the exhaustion of the immune system occurs- cell death and release of pro-inflammatory cytokines and cellular contents

Question 17

What are 2 viruses associated with HIV?

Answer 17

➝ Herpes simplex virus (HSV)

➝ Kaposi’s sarcoma herpesvirus (KSHV)

Question 18

What are 2 bacteria associated with HIV?

Answer 18

➝ mycobacterium tuberculosis

➝ salmonella

Question 19

What are 2 fungi associated with HIV?

Answer 19

➝ candida

➝ cryptococcus neoformans

Question 20

What are 2 parasites associated with HIV?

Answer 20

➝ cryptosporidium

➝ toxoplasma gondii

Question 21

What are the two possible routes of opportunistic infection in HIV?

Answer 21

➝ primary infection

➝ reactivation from latency

Question 22

What is a primary opportunistic infection in HIV?

Answer 22

➝ the infection is resolved by immune suppression and infection moves to the sites in the host that the immune system does not access
➝in these sites the virus resides without replication: latency

Question 23

When does reactivation from latency occur?

Answer 23

➝ upon immunodeficiency

Question 24

Describe how reactivation from latency occurs with HSV?

Answer 24

➝ HIV sufferers are exposed via the skin to HSV
➝ the virus replicates
➝ the virus gets into the infected host and moves into the nervous system
➝ there isn’t immune surveillance in the nervous system because the immune system can’t access the blood brain barrier
➝ the virus moves along the neurites into the dendrites
➝ The immune system is constantly surveilling so the immune system trying to interact with the cells is sending a constant message
➝ if the immune system is removed (HIV) the virus does not get the message so it is freed and goes back to the zone of infection
➝ the virus senses the lack of immune response

Question 25

Describe how reactivation from latency occurs with KSHV?

Answer 25

➝The virus enters and you get KS progenitor cells ➝They become de novo infections ➝De novo infection leads to latent infection of the immune cells (B cells) ➝KSHV gets into B cells and the immune system can’t see it ➝Latent infection -virus replicates at a low level ➝A cellular cue occurs - without the constant interaction between B cell and T cell the virus has no signal to reactivate ➝In a HIV sufferer there are no T cells so there is no constant signal between T and B cells which provides a reactivation signal to the virus

Question 26

Describe how KSHV can become carcinogenic?

Answer 26

➝There is infection of cells KS progenitors ➝De novo infections occur which turn into latent infections ➝There is some intra or extracellular cue which reactivates the virus ➝Such as inflammatory cytokines from pyroptosis ➝These cytokines may be the cues which reactivate the virus from latency ➝This leads to lytic or productive infections A few of these cells become oncogenic and undergo uncontrolled replication ➝During oncogenesis there is also an inflammatory response

Question 27

What therapy stops HIV replication?

Answer 27

➝ ART (antiretroviral therapy)

Question 28

What is ganciclovir?

Answer 28

➝ Direct acting antiviral drug which prevents KSHV replication within B cells

Question 29

What are the 7 viruses that cause cancer?

Answer 29

``` ➝ HPV - Human papilloma viruses ➝ EBV - Epstein-Barr virus ➝ HBV - hepatitis B virus ➝ HCV - hepatitis C virus ➝ HHV-8 - human herpes virus 8 ➝ HTLV-1 - human T lymphotropic virus-1 ➝ MCV - Merkel cell polyoma virus ```

Question 30

What type of a virus is HPV and what cancer does it cause?

Answer 30

➝ papilloma virus ➝ circular dsDNA ➝ skin cancer

Question 31

What type of a virus is EBV and what cancer does it cause?

Answer 31

➝ Herpes virus ➝ linear dsDNA ➝ lymphoma

Question 32

What type of a virus is Hepatitis B virus and what cancer does it cause?

Answer 32

➝ Hepadnavirus ➝ circular dsDNA ➝ carcinoma

Question 33

What type of a virus is Hepatitis C virus and what cancer does it cause?

Answer 33

➝ Flavivirus ➝ ssRNA ➝ carcinoma

Question 34

What type of a virus is HHV-8 and what cancer does it cause?

Answer 34

➝ Herpes virus ➝ linear dsDNA ➝ lymphoma

Question 35

What type of a virus is HTLV-1 and what cancer does it cause?

Answer 35

➝ retrovirus ➝ RNA-DNA ➝ leukemia/lymphoma

Question 36

What type of a virus is MCV and what cancer does it cause?

Answer 36

➝ Polyomavirus ➝ dsDNA ➝ carcinoma