Whitt-HIV Flashcards

1
Q

T or F: the steady increase in the prevalence of AIDS is due to more new cases occurring.

A

False, Antiretoviral Drugs have turned AIDS into more of a chronic disease so the increase is due to people living longer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

HIV is a member of what family of viruses?
• oncogenicity?
• Types, differences?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the 3 phase of an HIV infection?
• time span
• Symptoms
• what is the virus doing

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the best way to classify HIV?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

HIV
• Receptors (primary, co-receptors)
• Cell types infected
• Importance?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What important proteins does HIV carry inside its capsid?

• what about within the capsid/envelope?

A

Inside:
• Reverse Transcriptase
• Integrase
• Protease

In Capsid:
• gp120
• gp41
• p24

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the purpose of the HIV proteins present inside the capsid?

A

Reverse Transcriptase - converts ssRNA geome to cDNA

Integrase - integrates HIV genome into host genome

Protease - cleaves precursor protein into p24, p17, and p7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the purpose of the HIV proteins that are in the capsid/envelope?

A

gp120 - binds the receptor (CD4, CXCR4, CCR5)

gp41 - transmembrane protein essential for HIV envelope fusion with the host

p24 - makes up the capsid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What other proteins are cleaved from the same precursor protein that p24 is cleaved from?
• what enzyme does the cleaving?

A

p17, p7 and p24 are all cleaved from the same protein precursor by the HIV-protease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

HIV genome
• Size
• Layout

A

Size - 10 kb

Layout:
• Long-Terminal Repeats (LTRs)
• LTRs serve a promoters for mRNA synthesis of genome replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the function of the tat and Rev HIV proteins?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are nef, vpr, vpu, and vif?

• what is believed to the function of nef?

A
  • Contribute to Pathogenesis but are NOT essential

* ppl. who have nef mutations have slower disease progression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

T or F: HIV can enter CD4+ cells regardless of whether they possess CXCR4 or CCR5.

A

False, CD4+ is a necessary condition, but not a sufficient one to enter the cell. HIV NEEDS CXCR4 or CCR5 to enter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe membrane fusion of HIV with the host cell.

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What two drugs are given to prevent membrane fusion with HIV?
• How do these drugs work?

A

Enfuvirtide (T-20, Fuzeon)
• binds to gp41 and prevents membrane fusion

Maraviroc (Selzentry)
• binds to CCR5 and antagonizes it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What unique feature of HIV is responsible for its lifelong persistence?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the virus called once incorporated into the host genome?

A

Incorporated Virus = Provirus

• In provirus form HIV can’t be distinguished as foreign by our cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

After incorporation to the host genome, how does the provirus remain hidden?

A

Levels of tat (transcriptional activator) are low so gene expression goes at a really slow rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What factors drive HIV after emerging from its latent phase?

• early?, Late?

A

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

20
Q

T or F: after budding HIV is ready to infect a new host.

A

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

21
Q

What is the consequence of the high mutation rate seen in HIV?

A

• Cell Tropism Changes in the course of infection and viruses undergo selection do to host immune responses

22
Q

There is variation in Disease presentation and time to Disease Onset in HIV. This can be attributed to:
• Genetic Background
• Age
• Viral Strain

A

There is variation in Disease presentation and time to Disease Onset in HIV. This can be attributed to:
• Genetic Background
• Age
• Viral Strain

23
Q

T or F: IV drug use accounts for 1/4 of all AIDS infection.

A

True

24
Q

T of F: Whole blood, plasma, and clotting factors have all been known to transmit HIV.

A

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

25
Q

T or F: the use of anti-viral drugs during pregnancy is contraindicated.

A

False, 20-25% transmission rate if the mother is untreated, this drops substantially with administration of antivirals

26
Q

What is the rate of seroconversion for occupation HIV needle sticks?
• what should you do if stuck by a needle?

A

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

27
Q

When can a virus specific immune response to HIV be detected?

A

3 months after initial infection

28
Q

What are some common Protozoan infections seen in people with full-blown AIDS?

A
  • Pneumocystosis

* Toxoplasmosis

29
Q

What are some common Fungal infections seen in people with full-blown AIDS?

A
  • Histoplasmosis

* Candidiasis

30
Q

What are some common mycobacterial infections seen in AIDS?

A

DISSEMINATED TB

31
Q

How long to symptomatic AIDS pts. typically live if untreated?

A

~2 years

32
Q

What 2 criteria are used to predict disease progression?

A
  1. Loss of CD4+ T cells

2. Viral Load

33
Q

Why is the T cell count not completely indicative of immunocompetency in HIV pts?

A

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

34
Q

What 2 groups of people are in the 5-10% that are resistant to AIDS?
• what is this linked to?

A
  1. Elite Controllers - remain symptoms free WITHOUT therapy for 10-15 yrs post-infection
  2. 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

35
Q

T or F: the CCR5 gene is dominant

A

False, only homozygotes experience full resitance, heterozygotes only see slowed progression

36
Q

What serological two tests are used to detect HIV?
• What are they detecting?
• Confirmation of Dx?

A

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

37
Q

What 3 DNA based diagnostic assays are used to detect HIV?

• what are they detecting?

A

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

38
Q

What would you do for someone that lived with an HIV infected person or an IV drug user?

A

Give Pre-Exposure Prophylaxis with Tenofovir and Emtricitabine (reduces risk by 90%)

39
Q

What gene is most important in converting HIV from a latent state to an active state?

A

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

40
Q

T or F: HIV can infect a cell whether or not its nuclear envelope has been broken down.

A

True

41
Q

What is the job of RRE?

A

RRE is what Rev grabs onto to get the mRNA message into the cytoplasm

42
Q

T or F: HIV can still but if it lacks HIV protease.

A

True, but it will not be able to reinfect another cells because it lacks the protease

43
Q

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

A

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

44
Q

What does the oral dipstick test detect?

A

ANTIBODY made against the virus, NOT viral protein

45
Q

A delta 32 mutation is what cause CCR5 people to be RESISTANT to HIV infection

A

A delta 32 mutation is what cause CCR5 people to be RESISTANT to HIV infection