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63 Cards in this Set

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  • Back
AIDS- Acquired Immune Deficiency Syndrome
The disease acquired as a result of being infected with HIV-causes immune system deficiency making individual susceptible to MICROBES normally DESTROYED by immune system
Deficiency in immune system
HIV- making immune system susceptible to microbes it once used to kill
Opportunistic infection
MICROBE infection that doesn't cause disease in normal individuals
If a microbe causes an infection in certain individuals but not others
Opportunistic infection.
How many copies of RNA genome is present in HUMAN IMMUNODEFICIENCY VIRUS?
RNA virus: 2 copies of RNA genome in virus
Draw a diagram of HIV structure
Virus carries
REVERSE transcriptase
HIV correlation between structure and function
reverse transcriptase
These are important because they are VIRUS SPECIFIC and essential to proliferation.
Why is HIV/AIDS a serious problem?
1) high mortality of infected people (individual, death)
2) there is a long asymptomatic period associated with it of 2-15 years (Society- transmission/spread to others)
Globally in 2004 how many people were there living with HIV/AIDS
40 million
Globally how many deaths were due to HIV/AIDS in 2004
3 million
Globally, how many new HIV infections in 2004
5 million
In the US, how many new HIV infections are there per year
In the US, what is the number of people living with HIV/AIDS
1.2 million (with more than 400k with AIDS)
How many people with AIDs died in 2005
What is the percentage of people with HIV/AIDS not in care in the US?
What is the % of people infected with HIV that don't know it?
25% of people infected with HIV don't know it
What are the symptoms of initial HIV infection? What is the time period for these symptoms?
Enlarged Lymph Nodes

Month or Two after virus exposure
HIV infects what kind of cells in the immune system?
CD4 expresing cells, ie. T cells and macrophages
Virus infects CD4 infecting cells including
Helper T cells and macrophages
How does the virus affect CD4?
It binds to Cd4 T cells and causes Cell death

Compromises immune system.
Effect of virus on macrophages
They don't die, they become dysfunctional
Macrophages+ cytokines and Viruses
Dysfunctional macrophages alter the cytokines they originally are supposed to produce
Macrophage + A/g+ virus
Macrophages has variant antigen presenting properties.
Graph of the CD4 T cell count/micro Liter of blood
It takes time for HIV to destroy immune system.
1) Flu-like disease after infection
2) Seroconversion and asymptomatic face ~ 10 years
3) Symptomatic phase
4) Aids leasds to death
Two ways macrophages are affected by HIV
1) cytokine production altered
- wasting syndrome as example
2) antigen presentation is altered
What is wasting syndrome and what is it associated with?
Wasting syndrome refers to a loss of body mass or size, most notably muscle mass (sometimes referred to as "lean body mass").
What are the major players in immune response?
1) macrophages - ingest, kill and "notify"
2) CD4 T cells- interpret danger signals and direct the response- help CTL kill virus infected cells
3) B cells require T cell signals to produce toxic antibody (th2)
HIV Is a retrovirus so...
It can integrate into the host DNA
HIV LIfe cycle
1) Virus binds to CD4 and coreceptor on T cell or macrophage
2) Viral envelope fuses with cell membrane allowing genome to enter the cell
3) Reverse transcriptase copies viral RNA genome into ds DNA which is integrated into host DNA
4) T cell activation induces txn of provirus and translation of proteins
5) Particles ASSEMBLED and BUD from the cell
What does the virus need to bind and fuse with cell?
Co receptor
Fusion of virus with affected cell
How does reverse transcriptase play into life cycle?
RNA copies reverse transcribe to make RNA into ds DNA which is integrated into human DNA
Virus Ds DNA
Protected from degradation and passed on to ALL daughter cells
T cells die because
EXHAUSTED of producing tons and tons of viruses
Where is the immune response to HIV located?
HEAVILy located in lymphoid tissues, as this is where T cells are
How much can CTLs kill?
some of HIV virus, but never really gets rid of all virus because virus in cell escapes SURVEILLANCE
Describe graph of immune response to HIV
high initial amounts of infectious virus in plasma then decreases and then increases

HIV specific CTLs are present
First way virus escapes surveillance?
high mutation rate

RT and infidelity
estimated 1 bp/copy made of HIV genome
If Ab in T cells are specific for epitopes then
can kill those specific epitopes
but RT has high infidelity, so you can't kill all of them, because they are unrecognized
Antibodies can LYSE a virus after BUDDING but...
HIV can spread to neighbor cell when cells touch (mphage presents antigen to T cells)

This fusion allows virus to spread from one cell to next and ANTIBODIES don't have access to them.
Infected macrophages can spread to where?

Produces HIV RESERVOIRS in brain
what are the three drug targets for HIV?
reverse transcriptase that make RNA-DNA hybrid

2) integrase: dsDNA into provirus

3) protease: cleavage into proteins and maturation after release
When virus budds from cell, cannot infect other cells until when?
it goes through maturation stage in which protease cleaves off the surface
If you inhibit protease
Then virus cells can't mature and infect others
What is HAART
Highly Active AntiRetroviral Therapy
Triple Drug Cocktail
Triple Drug Cocktail
2 RT Inhibitors
1 Protease inhibitor

so to inhibit HIV replication in multiple places
How do the RT inhibitors work?
Nucleoside analogs (bases ATCG)

Retrovir= Zidovudine
HIVID= zalcitabine
What do the inhibitors of RT look like
thymidine- building block of DNA
RT inhibitors and thymidine similarities
Look like thymidine but don't have OH group
Why is OH group necessary in peptide formation?
OH group is necessary to hook on the next nucleotide to make your chain. So chain is terminated when you don't have hydroxyl
When you don't have hydroxyl gorup
The chain is terminated.
What are some drawbacks to HAART
1) strict timing for meds
2) not all respond (metabolism differences
3) price
4) Long term: cardio and heart disease (protease inhibitors)
5) drugs are made for precise fitting- RT mutation doesn't allow drug to work.
What are the side effects of these nucleoside analogs?
Nausea, headaches, anemia (tiredness, lower white counts, peripheral neuropathy (ddC), pancreatitis (DDI)
Side effects of nucleoside analogs
DNA polymerases

constantly proliferating cells including (RBC, epithelial cells)
What is peripheral neuropathy and what drug causes it?
Tingling in hands or knees ;

How much of the new HIV infections are drug resistant?

HIV coreceptors have mutation that prohibits expression because they don't have CCR5

So as a result no fusion. less susceptible to virus infection
Merck's Integrase inhibitor
ds-DNA into provirus is inhibited
T-20 Fusion inhibitor and mechanism?
Blocks virus fusion of the virus the cell fues with

Refrigerate and inject!!!!
What factors allow disease to progress?
Other infections... may activate HIV in cells by inducing proliferation

2) toxicity of infecting strain
3) evolution from less virulent to more pathogen via mutation (high RT infidelity)
What are the viral components of HIV
gp 160
T cells eventually die because
produce 10000s of viral particles