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Infection and immunity > 24. HIV > Flashcards

24. HIV Flashcards

1
Q

what type of virus is HIV?

A

as positive sense single stranded RNA retrovirus

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2
Q

what genus of retroviridae does HIV belong to?

A

lentivirus

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3
Q

what species does HIV infect?

A

Humans and primates

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4
Q

how many people have died as a result of HIV?

A

650 million

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5
Q

how many people are currently living with HIV?

A

40 million

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6
Q

what is the distribution of HIV?

A

uneven and changed over time
currently main effects southern Africa and low income countries

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7
Q

how many people contraced HIV in 2022?

A

over 1 million

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8
Q

what is HIV really ?

A

an umbrella term for different viruses HIV-1 and HIV-2

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9
Q

which HIV viruses is the pandemic strain?

A

HIV-1 group M and its subtypes

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10
Q

why are there so many groups of HIV?

A

natural evolution and origin events for each group of HIV

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11
Q

where do HIV-1 strains originate?

A

Chimpanzees and gorillas

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12
Q

where do HIV-2 strains originate?

A

Sooty mangabey monkey

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13
Q

what type of disease is HIV?

A

Zoonotic

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14
Q

what is the animal reservoir for HIV?

A

primates

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15
Q

how did cross species transmission occur in HIV?

A

due to the hunting of primates for food or keeping them as pets

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16
Q

Where do several of the HIV lineages come from ?

A

independant zoonotic infections

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17
Q

what is HIV-1 group M derived from?

A

SIVcpz from P.troglodytes (chimps)

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18
Q

what was the viral route HIV spread around the world?

A

emerged in the congo and then moved to haiti and the west coats of the USA
The virus got to Europe both from the USA and africa

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19
Q

why is the retrovirus membrane important?

A

for attachment and entry into the host cell

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20
Q

what does the retrovirus matrix do?

A

encloses the capsule and protects the genome

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21
Q

what are the 3 key enzymes in retroviruses?

A

Reverse transcriptase
Integrase
Proteases

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22
Q

what does reverse transcriptase do?

A

makes DNA from an RNA template

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23
Q

what does integrase do?

A

integrates the retrotranscribed viral DNA into the host genome and is the key to persistent infection

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24
Q

what do retrovirus accessory proteins do?

A

increase the infectivity of the virus usually as transcriptional activators
important for virus assembly
avoidance of the immune system

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25
Q

what is the final step in the viral life cycle?

A

cleavage of precursor proteins to activate them

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26
Q

what cells do HIV mostly infect?

A

CD4+ helper T cells

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27
Q

what does the virus binding to the CD4 receptor cause?

A

a conformational change in the the receptor that exposes the CCR5 co receptor

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28
Q

what is CCR5?

A

a CD4 co receptor that HIV also binds

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29
Q

what happens after CCR5 binding?

A

the virus enter the cell by fusing the membranes

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30
Q

what happens when the HIV viruses enters the t helper cell?

A

the viral membrane is degraded first and then the capsule degrades after it

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31
Q

what happens once the viral capsule is degraded?

A

the genome binds reverse transcriptase and makes DNA from the RNA

32
Q

what can reverse transcriptase make from ssDNA?

A

DsDNA

33
Q

what happens to reverse transcribed viral dsDNA?

A

it is bound by the integrase and taken into the nucleus through the nuclear pore
the integrase inserts the viral DNA into the host cell genome and the cell transcribes it as its own DNA

34
Q

where are the early viral proteins transported?

A

to the cell membrane and they are inserted

35
Q

what tend to be late viral proteins?

A

poly proteins made of several componenets - more complex virulence proteins

36
Q

where do the final proteins and mRNA end up?

A

at the host cell membrane to form a virion

37
Q

what is the final maturation step in the HIV life cycle?

A

key proteases activating the precursor proteins

38
Q

what is the cellular tropism for HIV?

A

main target: CD4+ T cells
other targets: phagocytes and CNS

39
Q

how does HIV spread around the body?

A

taken to the draining lymph nodes and then enters the bloodstream

40
Q

what can develop as a result of HIV infection?

A

acquired immune deficiency syndrome or AIDS

41
Q

when was AIDS first identified?

A

1981

42
Q

what is the HIV virus related to?

A

the first isolated human retrovirus Human T cell leukaemia virus

43
Q

where was HIV first isolated?

A

from a lymph node of a patient in Paris

44
Q

what are the 2 markers for diagnosing HIV?

A
  1. how much viral mRNA is in the blood stream to indicate how much viral replication is occurring
  2. how many CD4+ T cells are in the blood to indicate how many cells are being killed
45
Q

what happens to the T cell count during acute HIV infection?

A

initially goes down very quickly but the immune system can recover

46
Q

what happens during a latent HIV infection?

A

a game of immune cat and mouse of HIV killing immune cells and then immune system recovering which can last for years
Ultimately the T cell count decreases

47
Q

what happens when HIV comes out of clinical latency?

A

the threshold value of the amount of HIV per ml of blood is crossed and the immune system cannot control the infection.
T cell count decreases to the point of none left and death occurs

48
Q

what are the key events in HIV disease progression?

A
  1. primary infection usually as an STI
  2. infect the gut due to close proximity and high vascularisation
  3. high levels of virus in plasma and dissemination to lymphoid organ
  4. chronic HIV infection of lymph nodes and depletion of CD4+ T cells
  5. chronic immune activation due to HIV
  6. accelerated virus replication and rapid CD4+ T cell turnover
  7. destruction of the immune system
49
Q

how are CD4+ T cells killed during HIV infection?

A
  1. directly killed by the virus
  2. indirectly killed by immune exhuastion or other immune cells
50
Q

how does HIV replication cause CD4+ dysfunction?

A
  1. causes high turnover of cell leading to immune exhaustion
  2. due to death of T cells the rate of T cell proliferation is accelerated as well as the rate destruction
51
Q

what does the destruction of mature T cells and impaired production of T cell lead to?

A

AIDS

52
Q

How is AIDS defined?

A

presence of terminal HIV-1 infection
CD4+ t-cell count of under ~200 cell /µl of blood
presense of opportunistic infections that otherwise wouldn’t be a problem

53
Q

what does a lower CD4 T cell count mean?

A

higher likelihood of opportunistic infections that
results of infection is multi organ failure as the body cannot cope

54
Q

what are a few common opportunistic infections in HIV patients?

A

brain - cryptococcal meningitis
lungs - TB and pneumonia
skin - herpes
genitals - gential herpes, HPV, yeast infections

55
Q

what are the 2 types of different factors that effect progression to AIDS?

A

viral factors
host factors

56
Q

what are host factors effecting AIDS progression?

A

HLA alleles
immune function
genetic polymorphisms
natural resistance to HIV

57
Q

what are viral factors effecting AIDS progression?

A

defective viruses and genetic variability
type of HIV like HIV-2 can sometime cause AIDS but slower

58
Q

what can make someone resistant to HIV?

A

modified or lack of CCR5 receptor so the virus doesn’t bind properly

59
Q

what disease progression does heterozygous CCR5 mutation show?

A

delayed progression to AIDS

60
Q

what disease progression does homozygous CCR5 mutation show?

A

Resistance to HIV that use that receptor like most HIV-1

61
Q

what are long term non Progressor?

A

1-5% of the population get infected but never develop AIDS
they can help us know what defences are effective
Criteria:
10+ years of having HIV but not developing AIDS
low viral loads
immune cells remaining high

62
Q

What is ART?

A

Antiretroviral therapy

63
Q

what is ART used to do?

A

block retroviral replication at various different steps to prevent destruction of CD4+ T cells and disease progression
prevent transmission

64
Q

what does ART target?

A

viral attachment
fusion
reverse transcriptase
integrase
protease cleavage

65
Q

how does ART reduce transmission?

A

with no detectable viral replication the virus is not transmissible

66
Q

Generally why does HIV transmission occur?

A

lack of knowledge or medical care
most transmission happens because people don’t know they have HIV

67
Q

what is PrEP?

A

Pre-exposure prophylaxis
taken before HIV exposure
for people not yet infected but may lead a high risk lifestyle

68
Q

What is PEP?

A

post-exposure prophylaxis
taken after HIV exposure to prevent developing infection

69
Q

what are the WHO targets for HIV infections and treatments?

A

90% of people should be aware they are infected
90% of those aware should be on treatment
90% of those on treatment should have undetectable virus

70
Q

Are we meeting WHO goals for HIV?

A

No despite many more people receiving treatment

71
Q

what is a big problem in terms access to ART therapy?

A

the highest effected areas cannot afford or access ART treatment as the demand is higher then the supply

72
Q

what happens when ART treatment stops?

A

the virus starts replicating again and the virus takes hold again

73
Q

what is the limitation of ART?

A

it doesn’t treat the viral DNA already integrated into the host genome as it is too similar to distinguish

74
Q

how does ART therapy need to be given?

A

for life
properly to prevent resistance to mutation

75
Q

why don’t we have a HIV vaccine?

A
  1. due to the massive genetic diversity of HIV it is hard to find a single target
  2. we haven’t found a way to induce broad active antibodies that can neutralise the virus
76
Q

how diverse is HIV?

A

very
1 person with an active HIV infection can have more viral diversity in their body then all known influenza strains

Infection and immunity (22 decks)

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