lecture 4 - HIV Flashcards
What type of infection did HIV originate as?
Zoonotic
What is a zoonotic infection?
An infection in humans caused by a pathogen originating in animals
What are the 3 key groups of HIV-1?
HIV-1 M group, HIV-1 O group, HIV-1 N group
What type of virus is HIV?
Retrovirus, lentovirus
Is HIV a RNA or DNA virus?
RNA
How many copies of its RNA genome does HIV have?
2
Is HIV a ds-RNA or ss-RNA virus?
ss-RNA
What make up the envelope of HIV?
envelope glycoproteins (gp120 +gp41)
What surrounds the HIV genome?
Nucleocapsid
What are the essential enzymes in HIV replication and invasion into host DNA?
integrase, protease, reverse transcriptase
What is the process of HIV replication within a host cell?
Attachment, Fusion, Uncoating, Reverse transcription, Nuclear Import, Integration into host DNA, transcription, nuclear export, translation, assembly, budding, release, maturation
What cells does HIV bind to and destroy?
CD4 T cells/ T lympocytes
What is the purpose of reverse transcription when HIV enters a host cell?
Makes a DNA copy of the viral RNA genome which can then be integrated into the host genome for transcription & translation
What is the product of reverse transcription?
cDNA - complementary DNA
What enzyme is required for the integration of HIV cDNA into the host genome?
Integrase
What state must a host CD4 T cell be in to allow the transcription of HIV genes?
Activated
What transcription machinery is used for the transcription of HIV genes in a host T cell?
host machinery - RNA Polymerase II
What are the 4 key modes of HIV transmission?
sexual transmission, injection drug use, blood/blood products via transfusion, vertical transmission from mother to infant
What is the most common route of HIV transmission?
sexual transmission
Where is HIV found in the initial host when passed on sexually?
semen or mucosal surfaces
What type of sexual intercourse has the highest risk of HIV transmission?
receptive anal intercourse
Why do STIs enhance HIV transmission in a potential host?
Inflammation of mucosal surfaces results in increased recruitment of T cells so increased targets, ulceration allows HIV to get in more easily
What barrier does HIV cross to infect in sexual transmission?
mucosal barriers
What is the process of local amplification of HIV after crossing a mucosal barrier?
Sub-mucosal CD4+ T cells, macrophages & dendritic cells are infected
After local amplification of HIV occurs at the submucosa, how does HIV spread to the rest of the body?
Via the lymphoid tissue by infected CD4+ T cells and dendritic cells
What is the trend in CD4 T cell count from infection to 10+ years (assuming no treatment)?
Rapid decrease in early weeks of infection, before slight increase again until approx. a year where this is steady decrease over several years until death
What is the trend in HIV viral load from infection to 10+ years (assuming untreated)?
Dramatic increase in first few weeks before decrease again until approx. 1 year when there is a slow increase over clinical latency period until huge increase during AIDS development after ~8years
What is the observation of HIV infection in the intestine, and why?
Loss of lymphoid aggregates (intestine appears smooth), due to loss of memory CD4+ T cells
Why is there a drop in viral load, and increase in CD4+ T cell count after approx. 6 weeks of HIV infection?
Anti-HIV immune system can control viral replication to recover CD4+ cell count
What immune cells are particularly involved in the early anti-HIV immune response?
CD8+ T cells
Why do HIV-specific CD8+ T cells fail to effectively control HIV infection?
HIV is able to rapidly mutate, meaning mutants will no longer bind to the MHC class 1 on CD8 T cells, meaning they cannot be recognised and eliminated
Why does HIV have a high rate of mutation (3 reasons)?
1.) Reverse transcriptase & host RNA polymerase II both have poor proof reading ability
2.) High rate of viral turnover
3.) high intra-individual diversity
How does CD4+ HIV infection impair other immune processes?
CD4+ T cells need to help CD8+ T cell and B cell responses
What are the broadly conserved epitopes in HIV?
Epitopes that are conserved across strains so can be detected by the body and will not then mutate, allowing antibodies to develop
Is it possible for broadly neutralising antibodies for HIV to develop?
Yes, in 20% of patients, few conserved broadly neutralising epitopes exist and can be targeted by antibodies, however these antibodies fail to alter disease progression
What are the 2 key cellular reservoirs of HIV infection?
1.) latently infected CD4+ T cells
2.) Macrophages & dendritic cells
Why are latently infected CD4 T cells a cellular reservoir of HIV?
They are not activated so will not express antigen and are therefore invisible to the immune system. They do not transcript the integrated HIV genome so HIV will not replicate, until the T cell is activated
What are the 3 key reasons HIV infection is persistent despite immune response?
1.) high rate of mutation
2.) loss of CD4+ T cell help for CD8+ T cells & B cells
3.) latent infected cell reservoir
What factor leads to the development of AIDS, during HIV infection?
Depletion of CD4+ T cells, below 200 count
What does AIDS stand for?
Acquired ImmunoDeficiency Syndrome
What are the 3 periods of HIV infection?
Primary infection, Clinical latency, AIDS
Why does loss of CD4+ T cells lead to immunodeficiency & AIDS?
Loss of help to CD8+ T cells & B cells leads to increased susceptibility to infections and cancer
What cancer is common in AIDS?
Kaposi’s Sarcoma
What virus causes Kaposi’s sarcoma?
Herpes virus
What types of infections/disease are common in AIDS due to reduced CD8+ T cell function?
Intracellular infections (viral, protozoan), cancer
What CD4+ T cell count indicates AIDS?
<200cells/mm^3
