3 HIV Flashcards
what family does HIV belong to
Retroviridae family
how is cDNA replication intermediate made
RNA viruses which use RNA-dependent DNA polymerase (reverse transcriptase) to make a cDNA replication intermediate
what are the 4 HIV-1 groups
M
N
O
P
what is group M HIV-1
majority
cause of the global HIV-1 epidemic; many strains
what is group N HIV-1
non-O/non-M
what is group O HIV-1
outlier
what does HIV-2 cause
Non-pandemic
where is HIV-2 found
largely restricted to West Africa
why is HIV-2 restricted to West Africa
HIV-2 may less efficiently transmitted than HIV-1
which is most pathogenic
HIV-1
effect of HIV-2 infection - symptoms
HIV-2 infected persons seem to remain symptom-free longer than persons infected with HIV-1
what may protect against HIV-1
prior HIV-2 infection
what does HIV-1 give rise to
HIV-1 gives rise to Group M, which leads to HIV pandemic
HIV-1 gives rise to Group P, O and N
gene structure of HIV
Two copies of +sense RNA
Diploid genome – two copies of RNA, genomes can recombine = generate diversity
Surface of lipid membrane have spikes that allow it to attach to membrane
Long terminal repeats on ends
what are genes are present in all HIV
All have Gag, Pol and Env gene
what additional genes for HIV are there
HIV has additional genes that are involved in replication and that allow it to escape from normal protective mechanisms
HIV replication - replication and antiretrovirals
Virus bind to CD4
Virus enters where reverse transcription occurs
DNA made, integrated into host chromosome
- can stay dormant (rare)
or
- immediately start making new viruses – translation
Assembly of virus, viral budding – released from cell
how is variability formed
point mutations as reverse transcriptase has no proof reading capability
HIV against immune system
immune escape by changing/masking antigenic determinants
- CTLs and Abs
what causes resistance to anti-retroviral drugs
- Point mutations in enzymatic proteins
effect of point mutations in enzymatic proteins
> RT - resistance to nucleoside and non-nucleoside analogues
> Protease - resistance to protease inhibitors
what causes altered cytopathogenicity
Env mutations alter co-receptor usage
effect of Env mutations alter co-receptor usage
> Different cell tropism, eg. Macrophages, T-cells,
> Different tissue tropisms, e.g. brain
Transmission
Transcutaneous
Sexual
Vertical
Transcutaneous transmission
- IVDA
- Needle-stick injury
- Contaminated blood and blood products
sexual transmission
homosexual
heterosexul
vertical transmission
(mother-infant) (if child has HIV, will get AIDs very quickly)
Clinical Features of HIV Infection (progression)
- Acute Primary Infection Syndrome
- Asymptomatic Infection
- Symptomatic HIV Infection and AIDS
Acute Primary Infection Syndrome
Flu-like illness, with high levels of virus replication until the infection is brought under immune control
Asymptomatic Infection
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
Symptomatic HIV Infection and AIDS
The immune system ceases to function and disease progresses, resulting in death
Acute Phase HIV-1 antibody type
antibody negative
Acute Phase HIV-1 RNA antigen type
antigen positive
Acute Phase virus co-receptor
Virus usually uses CCR5 co-receptor
effect of HIV on cell count
HIV causes CD4 cell count to become low = 200/ul blood or less = clinical AIDS
effect of seroconversion - acute phase
- HIV-1 antibody positive
- Decreased viraemia (RNA , Antigen )
Asymptomatic Phase
Active replication within lymph tissue
Symptomatic Phase
General dissemination of virus
CNS, other non-lymph tissue
Symptomatic Phase
Opportunistic infections/tumours
TB, Kaposis sarcoma
what has an Inexorable battle between
the virus and the host
viral phenotypes
Transmission and Asymptomatic – virus that exists use CCR5
resistance to HIV infection
Homozygote 32/ 32 - CCR5
HIV-1-Exposed Seronegative Sex-Workers protection
Protection associated with rare HLA types
- Targeting highly conserved T-cell epitopes
how do viruses escape the immune system
Point mutations in key epitopes bound to HLA molecules (which are recognised by cytotoxic T-cells)
Some mutations neutral, but some induce fitness cost
what causes a large cost to virus to escape immune system
mutating epitopes recognised by the ‘protective’ HLA types results in large fitness cost to virus
