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FS III, Module I > 12. HIV > Flashcards

12. HIV Flashcards

1
Q

AIDS Transmission

____ > blood

____ > blood

  • ____ contact
    • anal intercourse
  • ____ use
    • contaminated needles
  • ____contact
    • anal intercouse
    • vaginal intercourse??
  • ____
  • ____ products
    • eliminated by serum tests
A

semen
blood

male homosexual
intravenous drug
heterosexual
congenital
contaminated blood
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2
Q

HIV INFECTS:
____-cells
which modulate the immune system.

____,
which serve to engulf foreign invaders i.e., bacteria and viruses.

• CD4 helper T-cells - centerpiece of immune system
	○ Destroying \_\_\_\_ responses and \_\_\_\_ responses (both arms of the immune system)
A

CD4 Helper T
macrophages
CTL
humoral

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3
Q

The Hallmark of HIV: It is a ____
RNA is reversed transcribed into ____

* Every HIV virus has \_\_\_\_ strands of RNA - they have nothing really to do with each other
* Virus unloads, loses coat protein, and then RT works (converts RNA to DNA)
* Double helix DNA integrates into \_\_\_\_of host cell > \_\_\_\_ or \_\_\_\_infection
A 
retrovirus
DNA
two
DNA
lytic
latent
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4
Q

There are 2 States of HIV INFECTION

____ INFECTION
HIV Infection results in lysis.
The T cell is killed.

____ INFECTION
HIV Infection results in integration of the viral genome into host cell DNA. The T cell is not killed.

• Some cells are lytic and some cells are latent
	○ Both events are \_\_\_\_ on at the same time
• Treat the patient, you can knock down the lytic infection, but you cannot remove the \_\_\_\_ (bc integrated into host DNA)
	○ Still harbor the virus in their \_\_\_\_
A 
lytic
latent
going
latent
chromosomal DNA
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5
Q

Retroviral life cycle: latent vs. active infection

In latent infection- retroviral genome is present but is not ____ viral genome or mRNA for structural proteins

• ds-DNA integrated into chromosomal DNA
	○ \_\_\_\_ DNA
• Similar bt latent and lytic - proviral DNA
	○ Active > making mRNA into protein > coat protein, and makes mRNA that'll be packagaed to be vrulent and then it buds out
A

transcribing

proviral

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6
Q

LYTIC INFECTION begins with HIV attacking cell

Cell under attack by ____

• \_\_\_\_ is much bigger than the HIV
A

HIV

cell

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7
Q

Lytic Infection

  1. Virus enters, and attaches to ____ (CD4, CXC4, CCR5)
    a. Has a lipid layer derived from last cell ____, and a protein shell (the center part) > the shell has to break open to release the payload to release the RNA
    1. Releasing the RNA
      a. Within the cytoplasm > conversion of single RNA that was contained within virus gets converted to ____ (reverse transcribed)
    2. Migrates to the ____ (the ds-DNA)
    3. Integrated into chromsomal DNA of host cell
    4. ____ > makes proteins, and another full length copy of RNA
    5. Assembled and then ____
      a. [NOTES]
A 
receptors
infected
ds-DNA
nucleus
lytic
released
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8
Q

WATCH THE VIDEO AGAIN MY BOY!

A

YES

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9
Q

Latent HIV Infection

• Goes from virus infecting to integration of chromosomal DNA
	○ Gets reverse transcribed, etc
• Latent until a \_\_\_\_, biochemical stressor (\_\_\_\_, cytokine) activates the latent cell into a lytic cell
A

stressor

hormonal

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10
Q

The HIV Provirus

* Provirus = integrated \_\_\_\_ HIV
* \_\_\_\_ flanking the transcript
* \_\_\_\_, how it enters the DNA and links it
* \_\_\_\_ = polymerase/RT
A

ds-DNA
cellular DNA
terminal repeats (TR)
Pol

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11
Q

Fascinating calculation:
If the length of human DNA can be considered to
be 3,000 miles, then
one HIV proviral DNA would be ____ feet

A

40

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12
Q

At some later time, the LATENT provirus can be activated to produce LYTIC infection

• Virus enters (two strands), one gets RT > same RT turns RNA into DNA and then it makes it another DNA
• \_\_\_\_ brings into nucleus and integrates and makes \_\_\_\_
• Transcription wihtin nucleus, the new RNA
	○ mRNA and new genomes
• \_\_\_\_ are made, and they bring in the new RNA and a new virus is created
A

integrase
provirus
capsids

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13
Q

Although HIV can reside as a latent provirus in some T-cells, there is always ____ HIV production in other T cells.

Thus, once a person is infected with HIV, they are always…. making new ____.

* Some lytic cells can also become \_\_\_\_ when they infect new cells
* A \_\_\_\_ of going latent to lytic
A

active
virus
latent
dynamic

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14
Q

What is the modern history of AIDS?

• '\_\_\_\_ - undiagnosed cases
• First US case - \_\_\_\_
• AIDs defined in 81 by the CDC
• \_\_\_\_ - virus was isolated > serological tests (ELISA/western blot)
• 85 - viral genome sequencing
• \_\_\_\_ > first drug for HIV (famous drug) in 86 > worked immediately, but then stopped working
	○ The virus \_\_\_\_ so quickly, so the virus turns into resistant mutants
	○ Need to use multiple drugs for this > bc you're going to have a population that is resistant to one of the drugs
		§ Currently use \_\_\_\_ drugs to treat at once
	○ Can have reactions to these
• \_\_\_\_inhibitor - makes the protein shell [NOTES]
• \_\_\_\_ therapy
A 
59
79/80
84
AZT
mutates
three
protease
HAART
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15
Q

Discoverers of HIV

____ (France) & ____ (USA)

A

luc montagnier

robert gallo

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16
Q

World-wide HIV/AIDS:
Since the start of the HIV/AIDS epidemic in 1981, 78 million have been infected with HIV.
____ million have died from HIV/AIDS.
Thus, globally since the start of the epidemic, ____% who have ever been infected
have died from HIV/AIDS

A

39

50

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17
Q

Epidemiology

At end of 2013, there were ____ million people world-wide living with HIV

A

35

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18
Q

HIV Statistics from the WHO
• In 2013, an estimated ____ million individuals worldwide were newly infected with HIV.
• ____ is the most affected region, with nearly 1 in every 20 adults living with HIV. ____% percent of all people who are living with HIV in the world live in this region.
• As of 2013 estimated 3.2 million children worldwide are living with HIV.
• About ____ children become newly infected with HIV each day.

A

2.1
sub-saharan
71
700

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19
Q

HIV/AIDS living persons: World-wide, women make up ____%

A

50

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20
Q

World-Wide
The majority of HIV-infected people word-wide (35 million )
do not know they are ____.

• They have early stage - harbor the virus, but the \_\_\_\_ can fight it off in the beginning
A

infected

immune system

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21
Q

The number of people living with HIV
rose from 8 million in 1990 to 34 million in 2010.

In 1996 HAART Therapy was Introduced, leading to a ____ in number of infections/year

• \_\_\_\_ - combination therapy
	○ Multiple drugs
	○ One is bad, two is better (statistically the virus having resistance to two it falls off), and \_\_\_\_ is the best (less likely)
A

plateau
HAART
three

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22
Q

Two Tests to screen for HIV. ____ and ____
Elisa is first and cheaper test.
Western blot is more expensive and confirmatory.

•\_\_\_\_ is first and \_\_\_\_ second
A

ELISA
western blot
ELISA
western

23
Q

Both ELISA and Western blot are similar
in that purified ____ proteins are reacted with
____ present in patients blood.

• You're not looking for virus when you do these tests > you're looking for a marker > the \_\_\_\_ (have been made as a result of your immune system having seen the HIV virus)
• HIV viral protein isolated in lab, and you take patient's blood > ask for antibodies against HIV (in both tests)
	○ Measuring \_\_\_\_ binding to pure \_\_\_\_ protein
A 
HIV
antibodies
antibodies
antibodies
HIV
24
Q

ELISA test to detect ____ to HIV in blood
Enzyme-Linked Immunosorbent Assay

• \_\_\_\_ reaction for an ELISA
	○ Upon antibody binding protein
• Have to \_\_\_\_ the testing
A

color

confirm

25
Q

Western Blot Analysis

* Confirm with the western blot
* Can separate out \_\_\_\_ proteins
* You get \_\_\_\_ bands (sporadic), match the \_\_\_\_ to know negative or positive
A

HIV

background

26
Q

CD4 Helper T cells mediate the immune response: they are at the “heart” of immune system

• CD4 mediate the response, they're at the heart of the response
	○ Mediates cell mediated and humoral response
• CTL mediated - infection of virus > quick response and it would kill it
• [NOTES]
A

NEEDS THE NOTES HERE MY BOY!

27
Q 
Question:
If someone is infected
with HIV, do they have AIDS?
Answer:
\_\_\_\_
Question:
Then, what is AIDS?
Answer:
AIDS is clinically defined
as having a \_\_\_\_ cell count of LESS than
\_\_\_\_ cells per ml of blood.
A

NO
CD4+ T
200

28
Q

Follow the events of HIV infection leading to AIDS and death

	• NO THERAPY
	• Starting Infection on left (blue)
		○ Weeks into years
		○ Body responds, and knocks the amount of \_\_\_\_ down, but its slowly eroding the immune system > immune system is depleted and then more \_\_\_\_ is made
	• CD4 cells (red)
		○ Contrast - as virus increases, then the \_\_\_\_ depletes; bc the virus is killing the CD4
	• Count (green) > \_\_\_\_
	• [NOTES]
A

virus
virus
CD4+
200

29
Q

HIV infected individuals do NOT get AIDS as long as their immune systems constantly replaces ____ cells destroyed by the virus

* Rate of water is so water is not above bowl, but its not draining - the water level is \_\_\_\_
* Drain - infection - killing off the CD4+
* Body keeps supplying what is lost
A

CD4+

constant

30
Q

Years later, AIDS occurs when the immune system cannot sustain ____ production, probably due to ____ or ____.

• On top of HIV, another infection going on at same time
• Go below \_\_\_\_ CD4+/ml
	○ Immune system is defeated
A

CD4+
illness
stress
200

31
Q

Oral Lesions assocaited with HIV infections!

Take a look at this, ya bitch!

A

YA

32
Q

One example….. Kaposi’s Sarcoma or KS

is often seen first in the ____

A

oral cavity

33
Q

Important Proteins of HIV

* Yellow around is the \_\_\_\_
* Blue dots = \_\_\_\_
* Green = membrane derived from last \_\_\_\_
A

shell
RT
infected cell

34
Q

Different points of HIV infected cell

  • ____
  • Reverse transcription and integration
  • ____
  • Assembly, budding and maturation• Can target any of these four steps
    ○ ____ and ____ are important targets
A

binding and entry
transcription and translation
protease
RT

35
Q

HIV vaccine approaches

  • recombinant protein (gp120)
  • synthetic peptides (V3)
  • naked DNA
  • live-vectored vaccine (bacterial, viral)
  • whole-inactivated virus
  • live attentuated

To date, not ____

A

successful

36
Q 
There have been many HIV vaccine Trials None have worked
• \_\_\_\_ vaccines.
• \_\_\_\_subunit protein vaccines 
• \_\_\_\_ vaccines
• Vaccine \_\_\_\_
• \_\_\_\_-like particle vaccine
A 
peptide
recombinant
live vector
combinations
virus
37
Q

HIV THERAPEUTICS:

Using ____ to control HIV INFECTION

A

drugs

38
Q

AZT: Inhibitor of RT

	• \_\_\_\_ - a regular nucleotide used in DNA synthesis
		○ All hooked to a \_\_\_\_ - the backbone
		○ \_\_\_\_ are sticking out
	• AZT
		○ Nothing changes about the base
		○ But on the ribose, the \_\_\_\_ is removed so the DNA chain cannot be elongated
			§ \_\_\_\_ group is inserted in its place
		○ Chain \_\_\_\_
	• But the virus \_\_\_\_ to it eventually
A 
ribose
nucleotides
3' OH
azido
terminator
mutates
39
Q

Single drug treatments produced Resistant HIV

AZT, the first HIV drug, was effective at first… but then after a while It no longer blocked infection efficiently due to viral ____.

A

resistance

40
Q

IMPORTANT QUESTION:
Why does a single HIV anti-viral drug stop working

ANSWER:
The Reverse Transcriptase has no ____ function.
There is a mis-incorporation of one in every ____ nucleotides (or one in every new ____ produced).
This gives rise to ____ strains:
An AIDS person may have:
1 million to 100 million variants of the HIV.

• Our genomes have an editing function - we have a polymerase, see a misincorporation of nucleotide, the pol backs up and recognizes it
	○ Removes and inserts the correct nucleotide
• A billion HIV a day, and every one is an alteration > getting a ton of mutants
A

editing
10000
HIV
resistant

41
Q

SOLUTION to Antiviral drug resistance:
Use a cocktail of drugs this is called:
____

A

Highly active antiretroviral therapy

HAART

42
Q

Here are different HIV protein drug targets

  • ____
  • HIV proviral DNA
  • ____
  • Integrase
  • ____
  • Protease
A

CD4 receptor
RT
TAT antagonists

43
Q

Some HIV Protease Inhibitors:
____
Ritonavir
____

These inhibitors block HIV-____ which is needed to cleave viral proteins made during infection for final assembly into ____.

A

indinavir
saquinavir
protease
new virus

44
Q

HAART: Highly Active Antiretroviral Therapy
HAART uses two or more inhibitors: e.g. against ____ and ____

• HAART introduced > deaths decreased immediately, but the people \_\_\_\_ with HIV is continuing to increase
A

RT
protease
living

45
Q

Why it is difficult to completely eliminate HIV in an infected person using HAART
(or an eventual vaccine) ?

ANSWER: Latent HIV provirus cannot be blocked by ____ or vaccine.. but can ____ later

* With drugs you're going after \_\_\_\_ infection
* [NOTES]
* Must stay on \_\_\_\_ to keep it inactive
A

drugs
activate
lytic
drugs

46
Q

M-Tropic and T-Tropic HIV

There are
\_\_\_\_ tropic (M-tropic)
and
\_\_\_\_ tropic (T-tropic)
strains of HIV
• Tropic - the virus will go towards infecting whatever \_\_\_\_
A

macrophage
T-cell
cell type

47
Q
  • M-Tropic HIV infects Macrophages which express ____ + ____
  • T-Tropic HIV infects Helper T-Helper cells which express ____ + ____• Co-receptors differ among each strain infected
A

CD4
CCR5
CD4
CXCR4

48
Q

____ are infected first because in the mucosal tissue that
HIV encounters first (vagina, rectum, mouth)
there is an abundance of Macrophages and
a negligible number of ____ cells

• During intercourse, the tissue there is mainly \_\_\_\_ - high number of macrophages vs T-cells
A

macrophages
CD4+ Helper T
mucosal

49
Q

____ are infected First
HIV crossing the mucosa of the genital Tract and infecting macrophages first and then and ____

• For virus to get in, they first infect the macrophages, and then T-cells and then they infect the \_\_\_\_
A

macrophages
T cells
lymph nodes

50
Q

The vast majority (up to 90%) of the initial HIV infection is ____. The M-tropic virus uses the ____ and ____ co-receptors.

Since in many instances, HIV is transmitted sexually, the mucous membranes of the genital and gastrointestinal tract provide an abundance of CCR5 expressing ____ and ____ cells which M-tropic HIV infects.

Following this primary infection, HIV travels to the regional ____, making contact with activated ____ cells expressing the CD4+ and CXCR4 co-receptors. At this stage, the T-Tropic HIV strains ____.

A

M-tropic
CCR5
CD4

macrophages
dendritic

lymph node
activated T helper
multiply

51
Q

A lymph node infected with HIV (seen as the scattered ____ particles)

The lymph nodes are a reservoir for ____ replication

A

white

HIV

52
Q

Question:
What accounts for the difference in the M-tropic and T-tropic HIV strains?

Answer:
The ____ receptors.
M-tropic HIV uses ____ in addition to CD4 T tropic HIV uses ____ in addition to CD4

A

chemokine
CCR5
CXCR4

53
Q

Amazing finding

Individuals having both copies of their ____ genes mutated, are naturally immune to HIV infection and AIDS

Mutated CCR-5 cannot bind to ____

(____% of the population are CCR-5 negative)

• 0.1% are resistant to \_\_\_\_ because they don't have a functioning CCR-5
	○ The macrophages have a defective one, so the virus cannot \_\_\_\_
A 
CCR-5
CD4
0.1
HIV
enter
54
Q

The origin of AIDS

• Origin is from ____
○ SIV - had for a long time
○ When man interacted with animals (in Africa), perhaps by killing of monkeys, certain people in tribes got sick, but bc tribes were isolated villages may have gotten wiped out without affecting people
○ Upon introduction of ____ anywhere, it spreads

A

simian monkey

traveling

FS III, Module I (14 decks)

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