HIV mutation and consequences Flashcards
(42 cards)
How many people live with HIV
approx 39 mil
in 2022
2/3 of people of all people with HIV live in Africa
Who is at risk of HIV
- Men who have sex with men (21%)
- IV drug users (13%)
- Sex workers and their clients
- Mother to child (0.7%)
What is the main transmission route for HIV
Heterosexual contact
-Greatest transmission rate
-49% of new infections
How long is HIV incubation period
2 – 4 weeks
What happens during the acute stage of HIV
sympotoms
-most people don’t know they have been affected
symptoms
-fever
headache
-rash
-sore throat
looks like a flu or cold
What happens to T cells and antibodies during acute infection
- C- D4+ T cells decline temporarily;
- CD8+ T cells increase temporarily > trying to increase viral replication
- anti-HIV-1 antibodies appear
What happens during the chronic infection
- HIV is asymptomatic/latent
- It is replicating at low levels
- Can last for a decade or longer (some progress faster)
What happens to CD4, 8 cells during chronic infection
CD4+ cells gradually decline; CD8+ cells largely unaffected;(numbers remain the same)
Antibodies evolve.
What happens when HIV begins advance to AIDS
the virus load greatly increases and CD4 T cell count drops
-people get weight loss
-Malignancies (EBV can start to replicate when immune cells drop, can get many EBV lymphomas)
-Can get neurological symptoms
What is AIDS
what happens to t cells, b cells
- CD4 T cell count drops below 200 cells/mm
- CD4+ T cell depletion, loss of helper function
- B cells decrease/dysregulation
- impaired NK cell function
- Causes an increased susceptibility to opportunistic infections
surivial is around 3 years after you get AIDS
What infections are opportunistic when someone has AIDS
- Cryptococcal meningitis
- Toxoplasmosis
- Pneumocystis pneumonia (PCP); Pneumocystis jirovecii
- Oesophageal candidiasis
- Certain cancers, including Kaposi’s sarcoma
How can HIV be transmitted and what factors can put people at risk
How can the virus be transmitted?
- Bodily fluids: blood, breast milk, semen, vaginal secretions
- Mother to child DURING pregnancy and delivery
What factors can put people at risk
- Unprotected anal or vaginal sex.
- Sexually transmitted infection (STI) such as syphilis, herpes, chlamydia, gonorrhoea and bacterial vaginosis. → lots of immune cells, greater risk of virus getting through
- Sharing contaminated needles, syringes and needles and drug solutions.
- Getting unsafe injections, blood transfusions and tissue transplantation, and medical procedures that involve are unsterile piercing, cuts
- Accidental needle stick injuries
How do we test for HIV in a lab
HIV antibody test
-can test antibodies in blood or oral fluids
Nucleic acid test
-using blood
-tests virus load
-only used for high risk exposures
Antigen/antibody test
-p24 antigen is made by infected cells, detected before antibodies
What are the different strains and types of HIV
HIV-1 and HIV-2
Tell me about HIV-1
where it comes from, and how much infectiosn it accounst for worldwide
95% of all infections worldwide
come from gorillas and chimpanzees
Tell me about HIV 2
where we find it, what its like, the groups, where it comes from,
how infectious it is
- concentrated in West Africa
- less infectious than HIV-1
- progresses more slowly than HIV-1, resulting in fewer deaths
- Derived from Sooty Mangabeys (a type monkey that carry SIV)
- 8 known HIV-2 groups,-> A&B pandemic
NNRTI drugs ineffective against HIV-2
HIV-2: more than 55% genetically distinct from HIV-1
Why do the subtypes of HIV matter
what are the subtypes
HIV 1 is more complicated
-its an RNA virus so it mutates every time it replicates
-has 4 groups M, N,O,P
-M most common
-M has subtypes A,B,C
Why does HIV 1 having so many subtypes problamatic
If you wanted to vaccine yourself against HIV, you would need a vaccine that would target all 4 subtypes
What is the structure of HIV
- has two molecules of reverse transcriptase, in virus capsid that it takes into the cell with
- Enveloped positive sense ssRNA virus
- Embedded in envelope are 2 key Glycoproteins called GP41 and GP120 (help with entry to cell)
- at the end of RNA they have integrase proteins
- Contains two + ssRNA per virus particle
- HIV is a Lentivirus (subgroup of retrovirus)
Describe the lifecycle of HIV
It attaches to the CD4 and fuses
-releases it virus partciles
- Viral RNA used to synthesize dsDNA by reverse transcriptase (RNA-dependent DNA polymerase)
- the fact that it has two copies of reverse transciptase, when it enters in the cytoplasm it is immedulaty converted into DNA by the viral reverse transcriptase
- this is then shuttled into the nucleus
- this then viral DNA, have intergase enables the virus DNA to integrate into the human genome
- that its why you cant get rid of it
What recpetor binds to teh CD4 receptor
GP120 binds to CD4 receptor on target cell
How does HIV bind and fuse into the cell
1.HIV binds to the surface of a CD4 T cell
2. the GP120 receptor will specifically interact with the CD4 receptor.
3.This triggers a conformation change in gp120 enabling it to bind to its coreceptor -> CXCR4
4.further changes in shape happen so that GP120 is moved our of the way,
5. GP41 can penetrate into plasma cell membrane of target cell
5.this helps brings the envelope of HIV closer to plasma membrane
6. Viral envelope is made up of plasma membrane of target cell (like a wolf in sheeps clothing)
7.this creates a pore through which viral capsid is delievered into the t cell
How does the virus replicate when in teh cell
- dsDNA is circularized and enters the nucleus
- dsDNA integrated into the host genome, catalysed by enzyme integrase
- so the host cell does the heavy lifting for you, every time the cell replicates
- HIV infection is now permanent
- HIV can either enter latency or enter into the productive cycle.
What happens in the productive cycle
- Pro-virus DNA transcribed into mRNA by host RNA polymerase and exported from nucleus.
- mRNA translated into proteins.
- Viral proteins are assembled into virions
- New progeny virus released by budding
- Virus particle matures and becomes infectious
- get a polyprotein,
- virus encodes protease, cleaves polyprotein into single proteins
- so that you an form the capsid
- matures the virus
