FMS Week 10: HIV Flashcards
1
Q
HIV is what type of virus
A
Retrovirus
2
Q
Gag genes
A
Viral structural proteins
3
Q
Pol genes encode
A
Viral Enzymes
4
Q
Env genes encode
A
Surface glycoproteins
5
Q
HIV regulatory proteins
A
- tat
- rev
6
Q
HIV accessory proteins
4 Listed
A
- vif
- vpr
- vpu
- nef
7
Q
HIV Virion Structure
- viral glycoproteins
- Viral Matrix
- 2 copies of viral single stranded (+) sense RNA Genome
- assoicated nucleocapsid protein
- Viral enzymes (protease, integrase, reverse transcriptase, accessory proteins)
A
8
Q
The HIV Life Cycle
6 Listed
A
- Binding and Fusion
- Reverse transcription
- Integration
- Transcription and Translation
- Assembly
- Budding
9
Q
The HIV Life Cycle: Binding and Fusion
A
The virus binds to CD4 receptor and a coreceptor (CCR5 and CXCR4) and initiated fusion with the cellular membrane
10
Q
HIV Tropism is largely defined by?
A
Receptor expression
11
Q
CD4 is expressed on?
6 Listed
A
- T helper cells
- macrophages
- monocytes
- DCs
- Eosinophils
- microglial cells
12
Q
CCR5 is ____________ tropic
A
Macrophage R5-tropic
13
Q
CCR5 is expressed on
3 listed
A
- many immune cells
in particular
- Memory T cells and Macrophages
14
Q
50% of HIV infected individuals only have …
A
R5-Tropic HIV
15
Q
CCR5Δ32 mutation
A
confers resistance to HIV infection
16
Q
HIV type that predominates early after transmission
A
R5-tropic HIV
17
Q
CXCR4 HIV AKA
A
T-cell (X4)-tropic HIV
18
Q
CXCR4 is expressed on
A
Naive T cells and DCs
19
Q
X4-tropic HIV is associated with
A
immunodeficiency
20
Q
X4-isolates are typically highly?
A
Cytotoxic
21
Q
The HIV Life Cycle: Reverse Transcription
A
The viral enzyme reverse transcriptase converts the viral RNA genome into dsDNA
22
Q
HIV Reverse Transcriptase proofreading activity Consequences
2 Listed
A
- Replication of the viral genome is an error-prone process
- ~1 base/genome is mutated per replication cycle
23
Q
The HIV Life Cycle: Integration
A
The viral enzyme integrase transports the viral DNA into the nucleus and inserts the viral genome into the host chromosomal DNA (this is referred to as proviral DNA)
24
Q
Proviral DNA AKA
A
when the viral genome is inserted into the host chromosomal DNA
25
Integration into the host genome allows the virus to establish a...
Latent State
26
The HIV Life Cycle: Transcription and Translation
3 Listed
* Viral mRNA is transcribed and translated using host cell machinery
* Viral proteins are synthesized as polyproteins
* Viral transcription only occurs in actively replicating cells
27
The HIV Life Cycle: Assembly
2 Listed
* Polyproteins are cleaved by the viral enzyme protease
* Viral RNA and enzymes are encapsidated by gag proteins (CA and NC)
28
The HIV Life Cycle: Budding
2 Listed
* The viral glycoprotein is expressed on the membrane of the host cell
* Immature viral capsid structures traffic to the cell membrane and bud from this surface
29
The HIV Life Cycle Figures
30
Anti-retroviral drug classes that interfere with essential steps in the viral life cycle
4 Listed
1. Entry inhbitors
2. RT inhibitors
3. Integrase inhibitors
4. Protease Inhibitors
31
Anti-retroviral drugs: Entry Inhibitors Drug Name and Target
2 Listed
* Maraviroc (CCR5)
* Enfuvirtide (viral gp41)
32
Anti-retroviral drugs: RT Inhibitors Drug Name and Target
2 Listed
* Nucleotide/nucleoside analogs
* Non-nucleotide inhibitors
33
Anti-retroviral drugs: Integrase inhibitors Drug Name and Target
1 Listed
* Raltegravir (Isentress)
34
Anti-retroviral drugs: Protease Inhibitors Drug Name and Target
~10 clinically approved
35
Clinical Course Stages of HIV Infection
3 Listed
1. Acute Phase
2. Clinical Latency
3. AIDS
36
Clinical Course of HIV Infection: Acute Phase Description
3 Listed
* Marked by a mild acute flu-like illness and an acute viremia
* These high viral loads then rapidly decrease
* Wide dissemination of the virus throughout lymphoid tissues
37
Clinical Course of HIV Infection: Clinical Latency Phase Description
5 Listed
* Typically absent clinical symptoms
* Low viral loads, strong debatable immunity
* Massive viral replication and turnover of infected T cells
* Disruption of lymphoid architecture
* A slow decline in CD4+ T cell numbers
38
Clinical Course of HIV Infection: AIDS Phase Description
3 Listed
* CD4+ T cell count \<200
* Dramatic Increase in plasma viral loads
* Increased susceptibility to opportunistic infection due to compromised B and T cell function
39
Routes of Transmission for HIV
3 Listed
40
HIV Trojan Horse
4 Listed
41
Productive HIV Viral infection is dependent on
Cellular Activation
42
HIV can only establish a productive infection in?
Activated T cells
43
HIV can infect
Activated and memory T cells by can only establish a productive infection in activated T cells
44
How do T cells become activated for HIV to establish a productive infection
The initial immune response to HIV infection provides a source of activated T cells allowing enhanced infection
45
HIV can infect activated and memory T cells that are positive for?
CCR5-positive cells
46
Infection of activated cells produces virions and causes...
More T cell activation
47
HIV can remain in a latent form in
long-lived memory T cells
48
Memory T cells found at high levels in
lymphoid tissues (especially the mucosal lymphoid tissues)
49
Mucosal T cells are typically...
activated and owing their stimulation to gut flora
50
CCR5-positive cells CD4+ location percentiles
* 20% of peripheral blood CD4+ T cells
* 80% of gut CD4+ T cells
* 10% of LN CD4+ T cells
51
\_\_\_\_\_\_\_\_ Lymphoid tissue is a site of HIV Replicaiton early in infection
52
Summary of early events upon HIV infection
3 Listed
* Depletion of T cells in gut-associated lymphoid tissue
* Immune responses against HIV may provide a source of target cells
* Nevertheless, viral replication is eventually controlled by host immune responses
53
Immune Responses against HIV
2 Listed
54
Virus specific Ab effective against
* Viral particles
55
Viral Specific Ab poor effectiveness against
Virally infected cells
56
Virus specific Ab not effective against
latently infected cells
57
Virus-Specific CTL Effective against
* Virus Infected cell
58
Virus-Specific CTL Not Effective against
2 Listed
* Latently infected cells
* Virus Particles
59
Clinical latency coincides with the?
Induction of anti-HIV antibody and CTL responses
60
Set point viral load is correlated with time to \_\_\_\_\_\_\_.
AIDS
61
Characteristics of Chronic HIV Infection
4 Listed
62
Viral Variation explanation
2 Listed
* Gradual loss of immune control
* Gradual increase in viral cytopathicity
63
Clinical Latency is not?
64
Humoral Immune Responses against HIV
5 Listed
65
Neutralizing antibodies in HIV
66
Clinical Latency is not?
67
Antibodies lose the ability to?
Neutralize Virus
68
Why is it so difficult to elicit broadly neutralizing antibodies against HIV?
HIV has evolved several strategies to escape humoral immune responses
69
Vaccines against HIV are based on?
Neutralizing Antibodies
70
Neutralizing Antibodies are likely ineffective at controlling HIV infection but...
There is still great interest in developing prophylactic vaccines based on neutralizing antibody activity
71
Major probles to HIV Vaccines
* Viral evolution
* HIV Variability
72
Summary of Humoral immunity and HIV
5 Listed
73
Cell mediated immune responses against HIV
2 Listed
74
In HIV patients \_\_\_\_\_% of all CD8 cells are HIV specific.
2-10%
75
CTL responses target?
Multiple Viral Proteins
76
Immune responses thought to be the most important for controlling viral replication.
CTL Responses
77
CTL Responses in HIV Properties
5 Listed
78
Why do CTL responses ultimately fail?
3 Listed
* Viral escape from CTL through mutation
* Viral gene product nef may downregulate MHC Class I
* Chronic stimulation CD8+ T cells can lead to loss of effector functions
79
Role of immunodominance in CTL escape
3 Listed
80
Immunodominance places individuals at risk for? And reason?
2 Listed
* Immune escape by epitope variation
* Epitope variation prompts a switch such that CTL response is directed against subdominant viral epitope which must be less efficient in stimulating T cells
81
82
CTL escape in early, intermediate, and late
83
HLA Types can be related to
more rapid or slower disease progression
84
CTL responses bad, good and ideal
ideal - no escape from CTL and is lethal to the virus (invariant region, virus isn't able to mutate or escape)
Good - the virus can escape however virus suffers a loss of fitness
Bad - virus can escape and at no fitness cost
85
Which epitopes do you target for CTL inducing Vaccines for HIV?
Could depend on HLA type
86
How do you get protection against multiple strains/viral variants?
2 Listed
* 9 Major HIV subtypes, with up to 30% sequence variation in env
* every amino acid could change everyday
87
HIV Vaccines designed to induce CTL responses Considerations
88
The initial immune response to HIV reduces the virus levels by?
About 100 fold but no further
89
HIV infection summary
3 Listed
90
Why does HIV infection lead to CD4+ T cell depletion?
Virus Mediated
2 Listed
91
Why does HIV infection lead to CD4+ T cell depletion?
Immune System Mediated
2 Listed
92
HIV doesn't cause disease, the __________ does.
Immune system does
93
The reason why HIv gets people sick is because
the adaptive immune responses against the virus
in absence of an adaptive immune response against the virus the virus causes no sickness
94
Gut barrier function followed by microbial translocation
* during HIV infection the gut is leaky
* immunostimulatory molecules can leak in an exacerbate the chronic inflammation in HIV
