Immunology - HIV infection Flashcards
Using which enzyme does HIV replicate inside cells?
Reverse Transcriptase
How many genes are inside the HIV genome?
9 genes that encode 15 proteins
What is the role of reverse transcriptase in HIV?
Converts RNA into DNA which can be incorporated into host cells’ genes
What are the two key glycoproteins encoded by the HIV virus?
gp120 (initial binding)
gp41( conformational change)
Which cell of the immune system is particularly affected by HIV?
CD4+ T cells
Recall the receptor and co-receptors for HIV on CD4+ T cells
CD4 receptors
CCR5 CXCR4 coreceptors
In people who have natural immunity to HIV, what antibodies may be present in serum?
Anti-gp120 and anti-gp41 (Nt) antibodies
How does HIV infection affect CD8+ T cells?
by affecting the function of CD4+ T-cells and antigen presenting cells that are required for proper CD8+ T-cell maturation, HIV is able to decrease the circulating pool of effector and memory CD8+ T-cells that are able to combat viral infection
How does HIV infection affect monocytes and dendritic cells?
Not activated by CD4+ T cells and so cannot prime naive CD8+ T cells
How does HIV affect immunological memory (2)?
CD4+ T cell memory is lost
CD8 memory cell not activated by antigen-presenting cell
Why is there so much variation/mutation in HIV infection?
lacks proof-reading mechanisms from cellular DNA polymerases
Why is HIV mutation within the host problematic (3)?
Escape from neutralising antibodies.
Escape from HIV-1-specific T cells.
Resistance and escape from antiretroviral drugs.
Recall the 7 steps of the HIV life cycle
- Attachment/Entry
- Reverse Transcription and DNA Synthesis
- Integration
- Viral Transcription
- Viral Protein Synthesis
- Assembly of Virus and Release of Virus
- Maturation
Which drug classes are capable of inhibiting the action of reverse transcriptase in HIV infection?
- Nucleoside analogues reverse transcriptase inhibitors
- Non-nucleotide reverse transcriptases inhbitors
Which class of HIV drugs can prevent integration of viral DNA?
Integrase inhibitors
Which HIV drugs can prevent modification of translated viral proteins?
Protease inhibitors
What is the median time of infection with HIV to AIDS development?
8-10 years
What does it mean if someone is an HIV exposed seronegative individual?
Partner of individual with HIV who remains uninfected
What are the 3 major markers used to monitor HIV?
CD8
CD4
Plasma viral load
What is long-term nonprogression of HIV?
individuals who are infected with HIV, but control the infection without antiretroviral therapy (ART).
individuals who have been living with HIV for at least 7 to 12 years and have stable CD4+
How can HIV be diagnosed (2)?
anti-HIV antibodies (ELISA) - screening test
Western Blot = Confirmatory test
How are CD4+ T cell levels measured in HIV infection?
Flow cytometry
What are the two methods of testing for ARV resistance?
Phenotypic = viral replication is measured in cell cultures under selective pressure of increasing concentrations of antiretroviral drugs (compared to wildtype)
Genotypic = mutations detected by sequencing amplified HIV genome (limited to sequencing RT and P)
Which drugs make up a HAART regimen?
Three or more ART drugs
When should HAART treatment be initiated?
Immediately on diagnosis
Give 3 examples of NRTI HIV drugs
Zidovudine
Lamivudine
Emtricitabine
Recall 2 examples of protease inhibitor HIV drugs
Indinavir
saquinavir
What class of drugs are dolutegravir & raltegravir?
Integrase inhibitor
Which drugs make up the HAART regimen initially?
2 NRTIs + PI
What CD4 count defines AIDS?
<200 cells/ mm3
Which drugs make up the atripla pill?
Emtricitabine + tenofovir + efavirenz
Which ARV is best to use in pregnancy?
Zidovudine
How can CD8+ T cells prevent HIV entry into cells?
Producing chemokines MIP-1A, MIP-1b and RANTES which block co receptors
Macrophage Inflammatory Protein-1 Alpha
does HAART elimiate HIV from body?
no - there’s a reservoir in CD4+ T cells
4 ways of preventing HIV spread?
Male circumcision (APCs in foreskin at a high density)
Condoms
PrEP (Truvada)
TasP (Treatment as Prevention – if on treatment, cannot transmit infection; i.e. U=U)
what type of virus is HIV
HIV is a retrovirus, which means it carries single-stranded RNA
contains reverse transcriptase
whats gag protein
major structural protein (of HIV-1
what is the 1st line screeening test for HIV and what is the confirmational test
Anti-HIV antibodies (ELISA) – screening test
Anti-HIV antibodies (Western Blot) – confirmation test
whats a non-neutralising atibody seen in the adpative immune response to HIV?
anti-p24
what predits disease progression?
initial viral burdern (set point)
who are rapid progressors & elite controllers?
Rapid progressors (10%) will take 2-3 years to develop AIDS (these are mainly seen in Africa)
Elite Controllers (EC) can suppress the viral replication
what does a positive test require?
A positive test requires the patient to have SEROCONVERTED (i.e. started to produce Ab) This happens after ~10 weeks incubation period
what type of drug is efiraverz? what effect does it have on amplodipine
non NRTI
also a P450 inducer
amlodipine wont work as well
3 outcomes of HAART
increases CD4 T cell count
controls viral replication
improvement in host defences
4 limitations of HAART
doesn’t eradicate latent HIV-1;
fails to restore HIV-specific T-cell responses;
high pill burden;
adherence;
threat of drug resistance
other than T lymphocytes, what cell type is primarily infected by HIV?
macrophages
a mutation in what cell surface receptor may confer immunity from HIV?
CCR5
HIV is made up of two main viral envelope proteins:
gp120 - This receptor is responsible for initial binding to CD4 and a co-receptor, such as the CCR5 receptor.
gp41 - Binding of gp120 exposes gp41.
gp41 then leads to fusion with the host cell membrane and viral entry into the cell.
Mutations in the CCR5 receptor confer immunity against HIV as the virus cannot enter cells to replicate.
outline the effects on HIV on the immune system
activated infected CD4 helper T cells die/anergised
therefore monocytea and dendritic cells arent activated and cant prime naive CD8 T cell
CD8 T cell and B cell responses lost as a consequence
CD4 T cell memory also lost
CTLs kill infected monocytes and dendritic cells
give an example of a NNRTI
efavirenz
give an example of a fusion inhibitor
enfuviritide
gve an example of an attachment inhibitor
maraviroc
