12. HIV Flashcards
AIDS Transmission
____ > blood
____ > blood
- ____ contact
- anal intercourse
- ____ use
- contaminated needles
- ____contact
- anal intercouse
- vaginal intercourse??
- ____
- ____ products
- eliminated by serum tests
semen
blood
male homosexual intravenous drug heterosexual congenital contaminated blood
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)
CD4 Helper T
macrophages
CTL
humoral
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
retrovirus DNA two DNA lytic latent
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 \_\_\_\_
lytic latent going latent chromosomal DNA
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
transcribing
proviral
LYTIC INFECTION begins with HIV attacking cell
Cell under attack by ____
• \_\_\_\_ is much bigger than the HIV
HIV
cell
Lytic Infection
- 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- Releasing the RNA
a. Within the cytoplasm > conversion of single RNA that was contained within virus gets converted to ____ (reverse transcribed) - Migrates to the ____ (the ds-DNA)
- Integrated into chromsomal DNA of host cell
- ____ > makes proteins, and another full length copy of RNA
- Assembled and then ____
a. [NOTES]
- Releasing the RNA
receptors infected ds-DNA nucleus lytic released
WATCH THE VIDEO AGAIN MY BOY!
YES
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
stressor
hormonal
The HIV Provirus
* Provirus = integrated \_\_\_\_ HIV * \_\_\_\_ flanking the transcript * \_\_\_\_, how it enters the DNA and links it * \_\_\_\_ = polymerase/RT
ds-DNA
cellular DNA
terminal repeats (TR)
Pol
Fascinating calculation:
If the length of human DNA can be considered to
be 3,000 miles, then
one HIV proviral DNA would be ____ feet
40
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
integrase
provirus
capsids
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
active
virus
latent
dynamic
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
59 79/80 84 AZT mutates three protease HAART
Discoverers of HIV
____ (France) & ____ (USA)
luc montagnier
robert gallo
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
39
50
Epidemiology
At end of 2013, there were ____ million people world-wide living with HIV
35
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.
2.1
sub-saharan
71
700
HIV/AIDS living persons: World-wide, women make up ____%
50
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
infected
immune system
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)
plateau
HAART
three
Two Tests to screen for HIV. ____ and ____
Elisa is first and cheaper test.
Western blot is more expensive and confirmatory.
•\_\_\_\_ is first and \_\_\_\_ second
ELISA
western blot
ELISA
western
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
HIV antibodies antibodies antibodies HIV
ELISA test to detect ____ to HIV in blood
Enzyme-Linked Immunosorbent Assay
• \_\_\_\_ reaction for an ELISA ○ Upon antibody binding protein • Have to \_\_\_\_ the testing
color
confirm
Western Blot Analysis
* Confirm with the western blot * Can separate out \_\_\_\_ proteins * You get \_\_\_\_ bands (sporadic), match the \_\_\_\_ to know negative or positive
HIV
background
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]
NEEDS THE NOTES HERE MY BOY!
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.
NO
CD4+ T
200
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]
virus
virus
CD4+
200
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
CD4+
constant
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
CD4+
illness
stress
200
Oral Lesions assocaited with HIV infections!
Take a look at this, ya bitch!
YA
One example….. Kaposi’s Sarcoma or KS
is often seen first in the ____
oral cavity
Important Proteins of HIV
* Yellow around is the \_\_\_\_ * Blue dots = \_\_\_\_ * Green = membrane derived from last \_\_\_\_
shell
RT
infected cell
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
binding and entry
transcription and translation
protease
RT
HIV vaccine approaches
- recombinant protein (gp120)
- synthetic peptides (V3)
- naked DNA
- live-vectored vaccine (bacterial, viral)
- whole-inactivated virus
- live attentuated
To date, not ____
successful
There have been many HIV vaccine Trials None have worked • \_\_\_\_ vaccines. • \_\_\_\_subunit protein vaccines • \_\_\_\_ vaccines • Vaccine \_\_\_\_ • \_\_\_\_-like particle vaccine
peptide recombinant live vector combinations virus
HIV THERAPEUTICS:
Using ____ to control HIV INFECTION
drugs
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
ribose nucleotides 3' OH azido terminator mutates
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 ____.
resistance
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
editing
10000
HIV
resistant
SOLUTION to Antiviral drug resistance:
Use a cocktail of drugs this is called:
____
Highly active antiretroviral therapy
HAART
Here are different HIV protein drug targets
- ____
- HIV proviral DNA
- ____
- Integrase
- ____
- Protease
CD4 receptor
RT
TAT antagonists
Some HIV Protease Inhibitors:
____
Ritonavir
____
These inhibitors block HIV-____ which is needed to cleave viral proteins made during infection for final assembly into ____.
indinavir
saquinavir
protease
new virus
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
RT
protease
living
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
drugs
activate
lytic
drugs
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 \_\_\_\_
macrophage
T-cell
cell type
- M-Tropic HIV infects Macrophages which express ____ + ____
- T-Tropic HIV infects Helper T-Helper cells which express ____ + ____• Co-receptors differ among each strain infected
CD4
CCR5
CD4
CXCR4
____ 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
macrophages
CD4+ Helper T
mucosal
____ 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 \_\_\_\_
macrophages
T cells
lymph nodes
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 ____.
M-tropic
CCR5
CD4
macrophages
dendritic
lymph node
activated T helper
multiply
A lymph node infected with HIV (seen as the scattered ____ particles)
The lymph nodes are a reservoir for ____ replication
white
HIV
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
chemokine
CCR5
CXCR4
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 \_\_\_\_
CCR-5 CD4 0.1 HIV enter
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
simian monkey
traveling
