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MIC 430 > Lec 13: HIV > Flashcards

Lec 13: HIV Flashcards

1
Q

(The Discovery of HIV/AIDS)
In 1981, doctors in New York were puzzled by…
Meanwhile, other…
Soon it was realized…

A

…8 cases of a particularly aggressive form of Kaposi’s Sarcoma, a form of cancer. Strangely, these cases were all in young homosexual men, when the sarcoma was usually seen in older people.
…gay men in US had a rare lung infection. A year later the medical community had realized that these conditions were in patients whose immune systems were severely damaged. They were the first patients in the West to be diagnosed with Aids.
…the disease known as “slim” in Africa was also Aids.

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2
Q

In 1987, the president of the _____ _____ and the prime minister of ______ announced a joint agreement:

A

United States
France

Agreement: Luc Montagnier of France and Robert Gallo of the US are the first to discover HIV in 83’-84’

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3
Q

2 types of human immunodeficiency virus:

A

HIV-1 & HIV-2

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4
Q

HIV1/HIV2 each evolved from

A

a different simian immunodeficiency virus (SIV).

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5
Q

HIV-1 =

HIV-2 =

We focus on…

A

HIV-1 =much more prevalent, & largely responsible for the AIDS pandemic
HIV-2 = less comon, & mainly restricted to West Africa.

…HIV-1.

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6
Q

HIV infection damages:

This condition is called:

A
  • the immune system, leaving the body susceptible to infection with a wide range of bacteria, viruses, fungi and protozoa.
  • acquired immune deficiency syndrome (AIDS).
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7
Q

However, SIVs appear to

A

not harm their natural primate hosts (monkeys).

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8
Q

Main objectives in fighting AIDS: (2)

A

development of anti-viral drugs

and vaccines

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9
Q

(HIV virion)
Has the general characteristics of…
BUT,…

A

…retroviruses described in the previous lecture

…in contrast to most retroviruses: the capsid is cone shaped.

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10
Q

HIV-1 and HIV-2 have genomes about __ __ in length.

The genomes encode:

A

9.3 kb

auxiliary genes in addition to gag, pol and env, and so the viruses are classed as complex retroviruses.

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11
Q

Auxiliary genes roles: (3)

A
  1. ) controlling virus gene expression
  2. ) transporting virus components within the cell
  3. ) modifying the host’s immune response.
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12
Q

HIV genome has

A

3 ORFs

All 3 reading frames are used and there is extensive overlapping

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13
Q

(HIV Attachment and Entry)

The cell receptor for HIV-1 is…

A

…CD4, found on several cell types, including helper T cells and some macrophages; CD4 T cells are the main target cells

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14
Q

(HIV Attachment and Entry)

CD4 T cells are

A

the main target cells

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15
Q

(HIV Attachment and Entry)

Site of attachment is the CD4 antigen found on a variety of cells:

A 
helper T cells
macrophages
monocytes
B cells
microglial brain cells
intestinal cells
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16
Q

(HIV Attachment and Entry)

The interaction of gp120 with the _____ and __-______ results in: (2)

A
  1. ) a dramatic re-arrangement of gp41

2. ) which proceeds to fuse the membranes of the virion and the cell.

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17
Q

Reverse transcription is primed by

A

tRNA

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18
Q

After reverse transcription has been completed…

A

the pre-integration complex, which contains host proteins as well as virus proteins, is moved along microtubules towards the nucleus.

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19
Q

There is evidence that integration of the provirus in a resting memory CD4 T cell may result in a

A

Latent infection

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20
Q

Latent infection cells can provide

A

a reservoir of infection that is significant for the survival of the virus in individuals receiving anti-retroviral drug therapy.

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21
Q

In many cells, provirus integration leads to

A

Productive infection

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22
Q

What happens in a Productive infection

A

2 phases of gene expression can be distinguished.

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23
Q

Early Gene Expression: (3)

A

Nef: Negative regulatory factor, but stimulates replication !!

Tat: Transactivator of transcription, enhances transcription

Rev: regulator of expression virion proteins

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24
Q

Late Gene Expression: (4)

A

Gag
Pol
Env
And other proteins such as Vif, Vpr, Vpu, etc.

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25
Q

(Assembly and Exit of virions)

All of the virus proteins in the diagram are incorporated into…

A

…new virions, along with two copies of the virus genome and cell tRNA.

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26
Q

(Assembly and Exit of virions)

The envelope is acquired by…

A

…budding from the plasma membrane.

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27
Q

HIV-1 variability is largely due to

A

reverse transcriptase
antigens/host cell range/drug resistance
surface protein gp120

28
Q

Reverse transcriptase has no

A

proofreading mechanism, resulting in a high error rate

29
Q

HIV variability includes

A

the antigens, the host cell range and resistance to drugs.

30
Q

The surface protein _____ is…

A

…highly variable,

presumably due to evolutionary pressure exerted by the immune response of the host

31
Q

DNA Replication error rate = RNA Replication error rate =

Rev Transcription error rate =

A

DNA = very low
RNA = high
Rev Transc = very high

32
Q

How many mutated bp are expected per day?

A

2 x 10^8-11 mutated bp/day

20 million-20 billion errors

33
Q

Each day, AIDS patient makes ___ new virions

A

10^10

34
Q

(HIV transmission)

Common Methods: (2)

A
  1. ) Having anal or vaginal sex

2. ) Sharing needles or syringes

35
Q

(HIV transmission)

Less Common Methods: (2)

A
  1. ) mother to child, birth, or breastfeeding
  2. ) being stuck with an HIV-contaminated needle or other sharp object
  3. ) Receiving blood transfusions, blood products, or organ/tissue transplants that are contaminated with HIV
  4. ) Being bitten by a person with HIV
  5. ) Contact between broken skin, wounds, or mucous membranes and HIV-infected blood or blood-contaminated body fluids.
  6. ) Deep, open-mouth kissing
36
Q

(Progression of HIV infection)

Shortly after a person becomes infected with HIV

A

there is a huge rise in viraemia (= concentration of virus in the blood), and in some people there is an illness resembling glandular fever or influenza

37
Q

viraemia =

A

= concentration of virus in the blood

38
Q

Shortly after infection the concentration of HIV in the blood…

A

…rises to a high level, then it falls to a detectable low level throughout the asymptomatic period, and rise again — onset of AIDS

39
Q

throughout the asymptomatic period…

A

…Extensive virus replication continues with estimates of more than 1010 HIV-1 virions produced each day.

40
Q

The HIV infection persists in spite of…

A

… immune responses against the virus.

41
Q

Cell types killed by HIV infection =

And what are they involved in?

A

= CD4 T cells and macrophages

= those involved in the immune responses; there is also evidence that non-infected CD4 T cells are killed by apoptosis.

42
Q

_____ evolves as HIV infection proceeds, producing =

A

Virus

= new antigenic variants that may not be recognized by the antibodies and T cells present.

43
Q

For a while, the body is able to tolerate the onslaught on the immune system by…
In the blood, the concentration of…

A

…rapidly replacing most of the cells that have been destroyed.
…CD4 T cells steadily declines until a point is reached where the level of viraemia rises sharply and AIDS develops.

44
Q

Characteristics of AIDS:

A
  • infections with pathogenic micro-organisms
  • brain disease
  • and/or cancer
45
Q

The most common types of cancer are those that are

A

associated with viruses,

such as Kaposi’s sarcoma (human herpesvirus 8) and non-Hodgkin’s lymphoma (EBV, HTLV, HHV8, etc.)

46
Q

HIV-2 infections are associated with: (3)

A

longer asymptomatic periods,
slower progression of disease and
lower rates of transmission

47
Q

Kaposi’s Sarcoma aka

A

(KS)

48
Q

Kaposi’s sarcoma =

How does It manifest?

A

rare cancer of the blood vessels that is associated with HIV.
It manifests as bluish-red oval-shaped patches that may eventually become thickened. Lesions may appear singly or in clusters.

49
Q

Possible Targets for Pharmacologic Intervention of HIV: (5)

A
  1. ) Virion-cell receptor interaction
  2. ) Reverse transcriptase (including RNase H activity)
  3. ) Integrase
  4. ) Protease (virus protease, not cell protease)
  5. ) Virion assembly
  6. ) Viral regulatory factors
50
Q

Targeting Reverse Transcription is based on

A

Nucleoside Based

51
Q

to extend to add phosphate group, you need
This is why…
t.f…

A

3’ hydroxyl group
…chain grows 5’ to 3’ direction
…scientists replace 3’ OH to something else

52
Q

Do the HIV drugs also inhibit host cell DNA synthesis? (2)

A
  • Host cells DNA polymerase has a much lower affinity than RT for the drugs, moreover, it has proofreading capability to correct the mistakes in DNA production.
  • RT, however, has much higher affinity towards the drugs and has no proofreading capability!
53
Q

Despite the progress in HIV treatment, there is no way HIV can be

A

eradicated from infected cells

54
Q

What can be used to edit an integrated HIV genome ?

A

CRISPR/Cas9 system

55
Q

CRISPR/Cas9 system functions: (2)

A
  1. ) suppress HIV gene expression by mutating the viral LTR, or targeting other genes necessary for HIV replication,
  2. ) excise HIV provirus from host cells
56
Q

The preparation of blood products can include…

A

…treatment with lipid solvents and detergents to destroy the virions of HIV (and other enveloped viruses, such as hepatitis B virus).

57
Q

The risk of HIV transmission (from a mother to her child) =

  • Higher levels of risk being associated with..
  • This risk can be greatly reduced by…
  • Although drug treatment reduces the risk of virus transmission to children, it does not…
A

= ~15-40%,
…breast-feeding.
…anti-retroviral drug treatment of the woman before and after birth.
…cure infected individuals

58
Q

Despite of much effort, there is no sign on the horizon of an…
There are a number of reasons for this…

A

…HIV vaccine suitable for mass immunization.
…including the ability of the virus to rapidly evolve multiple antigenic variants as a result of its high mutation rate.

59
Q

Difficult to make HIV vaccine paper example:

A

(Vaccinated monkey actually increased viral transmission)

60
Q

Currently no vaccine for HIV/AIDS, why?

How?

A
  • Vaccines designed to protect against HIV backfire, leading to an increase, not decrease, in new infections.
  • Vaccination increases the number of CD4+ T cells — helper T cells, and they are the targets of HIV, leading to increased HIV infection!
61
Q

Why can the natural hosts tolerate SIV?

A

Produce much less interferon alpha

62
Q

interferon alpha =

A

= an alarm signal to the rest of the immune system

63
Q

No significant immune response to the virus =

A

= no progression to AIDS

64
Q

Methods utilized to detect HIV: (4)

A
  1. ) Detecting antibody
  2. ) Detecting antigen
  3. ) Detecting viral nucleic acid – (ex: PCR)
  4. ) Virus in culture
65
Q

HIV Window Period =
ranges =
during that time =

A

= A period of time after a person is infected during which they won’t test positive
= 9 days - 3 months (depending on the person’s body and on the HIV test that’s used)
= a person can be tested HIV negative even though he/she is HIV positive

66
Q

Can you still catch HIV from someone who is in the window period?
In fact,…

A

YES

In fact, there is evidence that a person in the window period is more likely to pass the virus on.**

MIC 430 (22 decks)

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