5- Viral Pathogens II (HIV)

Question 1

what are the stages of a ‘typical’ course of HIV-1 infection?

Answer 1

acute phase
establishment of set viral load
clinical latency/ chronic phase
progression to AIDS

Question 2

describe the ‘typical’ course of a HIV-1 infection

Answer 2

acute phase - HIV infects individual, rapid increase in viral replication as virus establishes itself within the immune system
- flu-like symptoms = fever, sore throat - often not recognised as HIV

established set viral load - viral replication/ load decreases to a stable rate/ set point, slowly depletes CD4+ T cells

clinical latency/ chronic phase - viral replication at a lower rate, still depleting CD4+ T cells, asymptomatic

progression to AIDS - continuous depletion of CD4+ T cells leading to immunodeficiency - numbers get so low immune function is impaired
- higher risk for opportunistic secondary infections like pneumonia, or cancers
- life-threatening complications and depleted immune function = immunodeficiency

Question 3

what is immunodeficiency?

Answer 3

failure or absence of elements of the immune system

Question 4

how can HIV viruses be detected and quantified?

Answer 4

using real-time PCR - quantify number of HIV RNA genomes, use as a diagnostic

Question 5

how does HIV lead to immunodeficiency/AIDS?

Answer 5

HIV consistently targets, infects, damages and kills CD4+ T cells - depletes their numbers and their ability for immune response = immunodeficiency

HIV can also infect macrophages and dendritic cells, and creates chances for opportunistic infections/ cancers - worsens immunodeficiency

interplay between HIV replication, immune cell dysfunction and opportunistic infections leads to a decline in immune function = AIDS

Question 6

what are permissive T cells?

Answer 6

make up 5% of T cells - allow HIV to enter, replicate and produce new HIV virions

cells where infection is productive - permissive cells undergo intracellular and extracellular immune responses to fight infection before committing cell death via apoptosis

Question 7

what are non-permissive CD4+ T cells?

Answer 7

cells where viral production isn’t productive - allow HIV entry but stall viral replication by interfering with reverse transcription

undergoes intracellular immune responses, eventually commit cell death by pyroptosis

Question 8

how do permissive T cells die?

Answer 8

apoptosis

Question 9

how do non-permissive T cells die?

Answer 9

pyroptosis

Question 10

what is pyroptosis?

Answer 10

rapid cell lysis and the release of proinflammatory cytokines = leads to cell death

involves cell membrane rupture and releasee of cell contents into extrac. space

Question 11

intracellular immune responses to combat HIV - by permissive or non-permissive CD4+ T cells?

Answer 11

both

Question 12

extracellular immune responses to combat HIV - by permissive or non-permissive CD4+ T cells?

Answer 12

permissive (as well as intracellular)

Question 13

describe the intracellular immune response enacted by permissive and non-permissive T cells, and why it doesn’t help

Question 14

how does HIV hide in permissive T cells?

Question 15

describe the immune response enacted by permissive T cells, and why it doesn’t help

Question 16

describe the immune response enacted by non-permissive T cells, and why it doesn’t help

Question 17

describe how (chronic) inflammation, HIV replication and immunodeficiency feed into a cycle

Question 18

examples of HIV-associated/ opportunistic pathogens

Answer 18

certain type of fungi - e.g. Candida - and parasites
Mycobacterium TB
salmonella
KSHV/ HHV-8 = human herpes virus
HSV/ herpes simplex virus

Question 19

describe the emergence of opportunistic infections/ cancers with HIV/ AIDS - give an example?

Answer 19

through two routed - primary infection, and reactivation from latency

primary infection- individual infected with pathogen for the first time, can be asymptomatic or lead to symptoms
- immune system resolves symptoms but infection moves to sites beyond immune system detection = hides, goes latent

reactivation from latency - after a period of dormancy, reactivated when conditions favour viral infection (e.g. AIDS immunodeficiency) = leads to recurrence/ worsening of disease

e.g. KSHV presents with skin/ oral lesions during primary infection, enters dormancy, reactivates due to AIDS immunodeficiency and can lead to Kaposi’s sarcoma

Question 20

mechanism of herpes virus infection in HIV-infected individual

Answer 20

HIV infects individual, and in the early stages herpes virus also infects

herpes doesn’t want to be detected so it undergoes retrograde transport to hide in neuron cells - hard to mount an immune response against CNS nerve cells = remains latent in nerve cells

once immune cells has depleted from continued HIV virus progression - immunosuppression/ deficiency stage reached

herpes virus reactivates - emerges from CNS to soft tissues via anterograde transport and replicates to cause disease

Question 21

mechanism of KSHV infection in a HIV-infected individual leading to cancer

Answer 21

primary infection of KSHV in HIV infected or healthy individual - infects B cells specifically, transforms them to become long, thin KSHV sarcoma progenitor cells

KSHV becomes latent in B cells, evades immune detection and hides in epithelial cells

once HIV infected has depleted immune function significantly. KSHV reactivates from B cell latency and expresses oncogenic cancer-causing factors = forms a potential cancer cells = more KSHV viral replication with a limited T cell response = more infection and transformed/ cancer cells form

contributes to Kaposi’s sarcoma formation

Question 22

what is Kaposi’s sarcoma?

Answer 22

type of cancer that forms in the lining of blood vessels and lymph vessels

forms lesions/ cell growths on skin

Question 23

examples of viruses that cause cancer

Answer 23

HPV- skin cancer
EBV - lymphoma
hepatits B - carcinoma
hepatits C - carcinoma
human herpes virus - lymphoma