Whitt-HIV Flashcards
T or F: the steady increase in the prevalence of AIDS is due to more new cases occurring.
False, Antiretoviral Drugs have turned AIDS into more of a chronic disease so the increase is due to people living longer
HIV is a member of what family of viruses?
• oncogenicity?
• Types, differences?
Retroviridae family and Lentivirus Subfamily
Oncogenicity:
• HIV does not cause cancer but may presdispose you to it
Types:
• HIV-1 (most common, worldwide)
• HIV-2 (less Pathogenic, found in W. Africa and Asia)
What are the 3 phase of an HIV infection?
• time span
• Symptoms
• what is the virus doing
Acute Phase (3-6 wks post inf):
• Flu-Like Symptoms from viral dissemination
• Lymphadenopathy
• Lots of Virus Replication
Latent Phase (6-12 years):
• Asymptomatic Phase
• CD4 T cells rebound then decline steadily
• VERY HIGH LEVELS OF VIRAL REPLICATION, TONS OF T-CELLS KILLED EACH DAY
Symptomatic Phase:
• Immune Failure - death due cancer or opportunistic infection
• T cell count beloww 200
What is the best way to classify HIV?
Tropism - i.e. the receptors they look for when trying to enter a cell
***In the case of HIV its actually looking for certain co-repressors
HIV
• Receptors (primary, co-receptors)
• Cell types infected
• Importance?
Primary Receptor used by both Virus types is CD4, Tropism is determined by Co-Receptor Specificity
X4 Virus/T-Tropic:
• CXCR4- specific
• Found Mainly on helper T cells
R5 Virus/M-Tropic
•CCR5 - specific
• Found on Macrophages and Activated T-cells
What important proteins does HIV carry inside its capsid?
• what about within the capsid/envelope?
Inside:
• Reverse Transcriptase
• Integrase
• Protease
In Capsid:
• gp120
• gp41
• p24
What is the purpose of the HIV proteins present inside the capsid?
Reverse Transcriptase - converts ssRNA geome to cDNA
Integrase - integrates HIV genome into host genome
Protease - cleaves precursor protein into p24, p17, and p7
What is the purpose of the HIV proteins that are in the capsid/envelope?
gp120 - binds the receptor (CD4, CXCR4, CCR5)
gp41 - transmembrane protein essential for HIV envelope fusion with the host
p24 - makes up the capsid
What other proteins are cleaved from the same precursor protein that p24 is cleaved from?
• what enzyme does the cleaving?
p17, p7 and p24 are all cleaved from the same protein precursor by the HIV-protease
HIV genome
• Size
• Layout
Size - 10 kb
Layout:
• Long-Terminal Repeats (LTRs)
• LTRs serve a promoters for mRNA synthesis of genome replication
What is the function of the tat and Rev HIV proteins?
tat (transactivator of transcription):
• Enhances the Rate of trascription
• ESSENTIAL for converting Latent HIV to active, acute HIV
Rev (Regulator of Expression of Virion Prots.):
• affects Unspliced mRNA transport out of the nucleus
What are nef, vpr, vpu, and vif?
• what is believed to the function of nef?
- Contribute to Pathogenesis but are NOT essential
* ppl. who have nef mutations have slower disease progression
T or F: HIV can enter CD4+ cells regardless of whether they possess CXCR4 or CCR5.
False, CD4+ is a necessary condition, but not a sufficient one to enter the cell. HIV NEEDS CXCR4 or CCR5 to enter
Describe membrane fusion of HIV with the host cell.
- gp120 binds CD4 and undergoes conformational changes
- Conformational Changes allow for gp120 to bind CCR5 or CXCR4 co-receptors
- gp41 (fusion domain) undergoes conformational change after co-receptor binding that allows it to insert a HYROPHOBIC PEPTIDE into the host membrane
- gp41 then shoves a 6 helix bundle between two heptad repeats and membranes are now fused
What two drugs are given to prevent membrane fusion with HIV?
• How do these drugs work?
Enfuvirtide (T-20, Fuzeon)
• binds to gp41 and prevents membrane fusion
Maraviroc (Selzentry)
• binds to CCR5 and antagonizes it
What unique feature of HIV is responsible for its lifelong persistence?
- INTEGRASE allows the HIV genes to enter into Terminally Differentiated cells (most retroviruses require cell division)
- Insertion into these cells means the HIV genome can lay undetected in the Host forever
What is the virus called once incorporated into the host genome?
Incorporated Virus = Provirus
• In provirus form HIV can’t be distinguished as foreign by our cells
After incorporation to the host genome, how does the provirus remain hidden?
Levels of tat (transcriptional activator) are low so gene expression goes at a really slow rate
What factors drive HIV after emerging from its latent phase?
• early?, Late?
Early Phase:
• tat gets expressed at higher levels
• tat Drives transcription at high Rates so Viral Replication can occur
Late Phase:
• Rev responsive element (RRE) (gene sequence)
• RRE allows for Rev binding to mRNA and transport of mRNA coding for Structural Proteins OUT of the Nucleus
T or F: after budding HIV is ready to infect a new host.
False, HIV can infect a new host only after dimerization of protease from gag-pol allows for cleavage of CORE PROTEINS, which MUST be released for the virus to become infectious
What is the consequence of the high mutation rate seen in HIV?
• Cell Tropism Changes in the course of infection and viruses undergo selection do to host immune responses
There is variation in Disease presentation and time to Disease Onset in HIV. This can be attributed to:
• Genetic Background
• Age
• Viral Strain
There is variation in Disease presentation and time to Disease Onset in HIV. This can be attributed to:
• Genetic Background
• Age
• Viral Strain
T or F: IV drug use accounts for 1/4 of all AIDS infection.
True
T of F: Whole blood, plasma, and clotting factors have all been known to transmit HIV.
True, this accounts for 2% of HIV infections, but new incidence decreased substantially as a result of Ab. screening and Heat Treatment of clotting factors
T or F: the use of anti-viral drugs during pregnancy is contraindicated.
False, 20-25% transmission rate if the mother is untreated, this drops substantially with administration of antivirals
What is the rate of seroconversion for occupation HIV needle sticks?
• what should you do if stuck by a needle?
1/300 - risk when stuck
• You should be tested within hours of the needle stick and Drug Sensitivities should be checked before initiating post-exposure prophylaxis
When can a virus specific immune response to HIV be detected?
3 months after initial infection
What are some common Protozoan infections seen in people with full-blown AIDS?
- Pneumocystosis
* Toxoplasmosis
What are some common Fungal infections seen in people with full-blown AIDS?
- Histoplasmosis
* Candidiasis
What are some common mycobacterial infections seen in AIDS?
DISSEMINATED TB
How long to symptomatic AIDS pts. typically live if untreated?
~2 years
What 2 criteria are used to predict disease progression?
- Loss of CD4+ T cells
2. Viral Load
Why is the T cell count not completely indicative of immunocompetency in HIV pts?
HIV affects T cell:
• Ability to Recall Antigens
• Reactive Proliferation
• IL-2 production
**so while you still have a good number of T cells they may not function properly
What 2 groups of people are in the 5-10% that are resistant to AIDS?
• what is this linked to?
- Elite Controllers - remain symptoms free WITHOUT therapy for 10-15 yrs post-infection
- Long-Term Survivors - people who are still live after 10 years whether of not disease progression has occurred
many of these people have CCR5 mutations
some long term survivors have Nef mutations
T or F: the CCR5 gene is dominant
False, only homozygotes experience full resitance, heterozygotes only see slowed progression
What serological two tests are used to detect HIV?
• What are they detecting?
• Confirmation of Dx?
Serological Tests:
• ELISA
• Dipstick Test (look for double band)
**These are looking for p24
To confirm you need Western Blot
• p24 AND p120 must be seen here to be considered positive
What 3 DNA based diagnostic assays are used to detect HIV?
• what are they detecting?
PCR amplification
• Detects amount of provirus *Dna incirculating Lymphocytes
• Both Latent and Active Virus Detected
RT-PCR
• Detects Viral *Rna in plasma
bDNA (branched DNA)
• Detects BOTH viral *RNA in Blood AND Provirus *DNA in circulating lymphocytes
What would you do for someone that lived with an HIV infected person or an IV drug user?
Give Pre-Exposure Prophylaxis with Tenofovir and Emtricitabine (reduces risk by 90%)
What gene is most important in converting HIV from a latent state to an active state?
Tat - this would be a good potential drug target to keep viral loads down
Note that LTR can’t be used as a promoter until tat is activated
T or F: HIV can infect a cell whether or not its nuclear envelope has been broken down.
True
What is the job of RRE?
RRE is what Rev grabs onto to get the mRNA message into the cytoplasm
T or F: HIV can still but if it lacks HIV protease.
True, but it will not be able to reinfect another cells because it lacks the protease
Imprortant for the Progression of HIV
• Continuous CD4+ depletion even in latency
• Continuous Viral Replication even in the asymptomatic phase
• Loss of CD8+ functioning as a result of macrophages being infected
• Loss of IL-2 production
Imprortant for the Progression of HIV
• Continuous CD4+ depletion even in latency
• Continuous Viral Replication even in the asymptomatic phase
• Loss of CD8+ functioning as a result of macrophages being infected
• Loss of IL-2 production
What does the oral dipstick test detect?
ANTIBODY made against the virus, NOT viral protein
A delta 32 mutation is what cause CCR5 people to be RESISTANT to HIV infection
A delta 32 mutation is what cause CCR5 people to be RESISTANT to HIV infection
