Lecture 16 (9B) - HIV Flashcards

Question

The replication of HIV

Answer 1

1. absorption to CD4 and co-receptor 2. fusion with cell 3. penetration 4. reverse transcription 5. integration 6. transcription 7. translation 8. capsid assembly 9. budding 10. maturation into cyto, RNA reverse transcribed to DNA, DNA into nucleus, replicated, into cell membrane and takes some of membrane with it

Answer 2

CD4 | and CCR5

Answer 3

CD4 and a chemokine receptor to infect target cells (CXCR4/CCR5) • CXCR4 on lymphocytes • CCR5 on lymphocytes and macrophages

Answer 4

the most important coreceptors used by HIV-1 in vivo are CXCR4 expressed on lymphocytes and CCR5 expressed on lymphocytes and macrophages • T-tropic isolates use CXCR4 • macrophage tropic isolates use CCR5 • dual tropic isolates use both

Answer 5

* individuals with a mutation in the CCR5 gene delta35 in both alleles are largely resistant to infection by HIB * those with a heterologous mutation in only a single allele suffer less disease * drugs that inhibit entry through CCR5 reduce viral load a man with HIV needed bone marrow transplant but had HIV, donor with a mutation in CCR5 --> CCR5 not on cell surface, has no HIV

Answer 6

proteins cleave it

Answer 7

CD4 lymphocytes and macrophages

Answer 8

• CD4+ T cells licence DC for stimulation of CD8+ T cells CD4 for T cell help (antibodies)

Answer 9

dendritic cells | • HIV binds receptor on DC, meets CD4 --> HIV given to the CD4 cell

Answer 10

• primary infection - immediate huge dip in T cells, huge increase of virus RNA - primary infection , seeding of lymphoid organs/brain, dissemination * clinical latency - T cells decreasing, RNA virus increasing (0.1 log per year rise in HIV load) * around 5/6 years get AIDS and opportunistic infections, T cells almost 0

Answer 11

* uncontrolled viral replication leads to marked cell mediated immune response * increased numbers of activated CD4 and Cd8+ cells expressing CD38, CD45R0, and HLA-DR * increased number of NK cells * elevated concentration of immune markers * increased concentration of cytokines: IFN-γ, TNF-α, ILK-1β

Answer 12

flu-like illness, with high levels of virus replication until the infection is brought under immune control

Answer 13

no outward sign of disease although there is a slow decline in the CD4 count, and very active viral replication • this stage can persist for 10+ years

Answer 14

the immune system ceases to function and disease progresses, resulting in death

Answer 15

10hr doubling time with peak viremia at 21 days • each infected cell seeds 20 infected cells • virus load drops rapidly as the immune response kicks in

Answer 16

* 10^10 virus particles made and eliminated daily * 10^9 CD4+ T cells made and eliminated daily * virus replication and elimination are nearly in equilibrium (steady state)

Answer 17

* approximately 10^6 - 10^7 T cells sustain the HIV-1 infection (productively infected, activated T cells) * the sze of the latent HIV-1 reservoir is similar

Answer 18

stable CD4 count for > 10 years • no disease symptoms • account for up to 5% of HIV infected people

Answer 19

* host factors - genetic factors that confer resistance (CCR5D32 mutation), ability to mount very strong immune responses to the virus * viral factors - infection with attenuated viral strains

Answer 20

* cytotoxic T cells | * neutralizing antibodies

Answer 21

• DC with MHC-I and viral peptide • TCR recognizes = activated/armed CD8+ cytotoxic T cells

Answer 22

is not needed once the cytotoxic T cell is armed | • repeat killing can then occur

Answer 23

• inducing apoptosis of infected cells is the main way CD*+ CTl eliminate infection • also contribute by producing cytokines: IFNγ TNFα LTα IFNγ • increases MHC-I expression • upregulates antigen processing machinery • increases macrophage recruitment and activation

Answer 24

* increases MHC-I expression * upregulates antigen processing machinery * increases macrophage recruitment and activation

Answer 25

* virus specific CD8 cells have been found in individuals exposed to HIV-1 but remain uninfected * after interruption of HAART preservation of CD4+ helper T cells is associated with the virus * depletion of Cd8+ T cells results in loss of viral control in SIV infected monkeys * HIV-1 CD4+ and Cd8+ T cells are preserved in LNTPs and the memory population are poly-functional and similar to that of EBV or CMV induced responses

Answer 26

1. agglutination 2. neutralization 3. opsonization 4. complement activation 5. antibody dependent cellular cytotoxicity (ADCC)

Answer 27

crosslinking by antibodies creates larger particles that are taken up more efficiently by phagocytes

Answer 28

antibodies can block attachment of pathogens to receptors on cells

Answer 29

FcR mediated uptake enhances pathogen clearance by macrophages and neutrophils

Answer 30

``` classical pathway alternative pathway lectin pathway • make C3 --> C3 convertase --> C3a and C3b --> C3b + C5 --> C5 convertase --> C5a and C5b C5b + C6-9 --> MAC (membrane attack complex) ```

Answer 31

* infected cell puts virus antigen on surface * antibodies stick to the antigen on the surface * NK cell or macrophage has receptor for Fc part of antibody * come together * NK cell or macrophage release particles that destroy virally infected cell

Answer 32

* passive immunization of chimps with neutralizing antibodies protects (but chronic establishment infection) * low levels of SIV viral load are associated with high levels of neutralizing antibodies in chronic infection * rapid escape from neutralizing antibodies in infected cells * neutralizing antibodies are the immune correlate of protection from infection (rather than disease as in CTL)

Answer 33

for a given virus population, the genome sequences cluster around a consensus or average sequence but every genome can be different wild type with genome space of possibilities

Answer 34

clade C, A, and AG

Answer 35

• 2003 the first AIDS vaccine of envelope protein to undergo a major trial is found to be ineffective • 2007 Step AdV trial of capsid protein - possible increased risk • 2009 RV144 trial of ALVAC canarypox capsid envelope gp120 prime boost - 16,000 Thai volunteers - possible slight protection 2013 - HTNV505 - halted by Data and Safety Monitoring Committee

Answer 36

* a cell type or site within the body where the HIV accumulates and persists with greater stability than the main pool of actively replicating virus * a reservoir is termed latent if the cells that harbour the virus are not actively producing virus but retain the capacity to do so * the reservoir may be resilient to eradication because of poor penetration of ARVs or special biological properties of the compartments such as being an immuno privileged site

Answer 37

brain and CNS are a reservoir for HIV infection

Answer 38

may be a reservoir for HIV | • in the acute phase of infection, HIV depletes the gut's CD4 immune cells and their numbers never bounce back

Answer 39

• a patient with the lowest level of the reservoir measured during ART 1 infected cell / 1.700,000,000 CD4s • rebound occurred after ART cessation

Answer 40

* activate the dormant viruses and encourage the body's immune system to attack them * we need to reconsider immunological interventions as complementary it ART * IL-15 target memory CD8 T cells and increase the survival of these cells * neutralizing antibodies * gene therapy interventions

Answer 41

* so far drug therapy can't cure HIV * no restoration of functional immunity, the damage is already done shortly after acute infection * the replicative capacity of the virus is never overcome

Answer 42

* eradication of the latent reservoir * gene engineering an HIV resistant immune system * therapeutic vaccination * gene engineering an HIV resistant immune system - a stem cell-based approach to treating HIV infection

Answer 43

* heterologous transplant of HSC from delta32/delta32 patient * viral clearance * phase I trials with 2 patient cohorts (1 for which therapy has failed, the other doing well)

Answer 44

* individuals with a mutation in the CCR5 gene in delta35 in both alleles are largely resistant to infection by HIV * those with a heterologous mutation in only a single allele suffer less disease * drugs that inhibit entry through CCR5 reduce viral load

Answer 45

Cd4 lymphocytes and macrophages

Answer 46

* can reconstitute immune cells for long periods | * amenable to genetic manipulation (antigen recognition or insensitivity to infection, probably both)

Answer 47

introduce delta32/delta32 mutations in the CCR5 gene | • introduce cellular restriction factors

Lecture 16 (9B) - HIV Flashcards

(72 cards)