HIV Flashcards
Distribution of HIV types
Twi types. HIV1 and 2
- HIV 2 geographically confined in ….. ………
Three groups of HIV1 isolates recognised:
- ..,… (major) and … (0ther)
- Most belong to group M which has at least 10 further subtypes
Subtle genetic differences and range of geographical distributions
Two types. HIV1 and 2.
HIV2 geographically confined to Western Africa.
Three groups of HIV1 isolates recognised:
N, M (major) and O (other).
Most belong to group M which has at least 10 further subtypes.
Subtle genetic differences and range of geographical distributions.
HIV structure
Enveloped ……. strand ….. retrovirus of family lentivirinae
Consists of ……. envelope surrounding a capsid containing a double stranded …….. sense RNA genome.
Also contains reverse transcriptase and ……… enzymes and two cellular transfer ….. molecules based ….. to th egenome in the …… core
Enveloped positive strand RNA retrovirus of the family lentivirinae.
Consists of glycoprotein envelope surrounding a capsid containing a double stranded positive sense RNA genome.
Also contains reverse transcriptase and integrase enzymes and two cellular transfer RNA molecules base paired to the genome in the protein core.
HIV structure
All retroviruses have some genes in common - … group specific antigen
pol - Polymerase:reverse transcriptase
env- envelope: glycoproteins
Needs a viral …… to cleave … and form ….-pol polyproteins after release from cell
releases the … and is necessary for producing infectious v……
All retroviruses have some genes in common - gag group specific antigen
pol - Polymerase:reverse transcriptase
env - envelope : glycoproteins.
Needs a viral protease to cleave gag and gag-pol polyproteins after release from cell.
Releases the RT and is necessary for producing infectious virions.
HIV structure
The envelope ….., gp …. and gp… and the core protein … are immunogenic and antibodies raised to these form the basis of the a…….. detection methods
Antibodies develop slowly
- .-. weeks at least and so detection of …. antigen or viral RNA are better to diagnose recently infected individuals
The envelope glycoproteins, gp 120 and gp41 and the core protein p24 are immunogenic and antibodies raised to these form the basis of the antibody detection methods.
Antibodies develop slowly,
4-8 weeks at least and so detection of p24 antigen or viral RNA are better to diagnose recently infected individuals.
HIV pathogenesis
Tissue tropic for CD4 cells and cells of the macrophage lineage
Binds to target cell CD4 receptor via …… and a …….. co-receptor
- Co receptor …..
Initially infects macrophages via CD4 and CC CKR5 receptors. Persistent infection
Enters cell b fusion of the viral envelope with the cell plasma membrane
Tissue tropic for CD4 cells and cells of the macrophage lineage.
Binds to target cell CD4 receptor via gp120 and a chemokine co-receptor.
Co receptor CXCR4.
Initially infects macrophages via CD4 and CC CKR5 receptors. Persistent infection.
Enters cell by fusion of the viral envelope with the cell plasma membrane.
HIV pathogeneisis
In the cytoplasm the transfer …. is used a a …. to synthesise cDNA using reverse transcriptase
cDNA is transported to the …… and spliced into the hose genome by ………..
Viral cDNA then transcribed as a …… …. to produce viral proteins and copies of the viral …. ……..
In the cytoplasm the transfer RNA is used as a primer to synthesise cDNA using reverse transcriptase.
cDNA is transported to the nucleus and spliced into the host genome by integrase.
Viral cDNA then transcribed as a cellular gene to produce viral proteins and copies of the viral RNA genome.
HIV Pathogenesis
HIV protease cleaves the proteins so that they can be assembled with the ….. RNA into new ….. to from the …..
- Cell ….
Reverse transcriptase makes many copy errors,
- 1 per 2000 bases transcribed
Genetic instability results with many ……… and new strains within one patient
HIV protease cleaves the proteins so that they can be assembled with the viral RNA into new viruses to bud from the cell.
Cell dies.
Reverse transcriptase makes many copy errors, 1
per 2000 bases transcribed.
Genetic instability results with many mutations and new strains within one patient.
HIV - pathogenesis
Killing of target cells dependant on amount of ….. expressed
High levels of virus in blood
- infected individuals have initial flu-like or ……. type infection
…. antigen and then ……….. production of antibody
Killing of target cells dependent on amount of CD4 expressed.
High levels of virus in blood.
Infected individuals have initial flu-like or mononucleosis type infection.
P24 antigen and then seroconversion to production of antibody
HIV - Pathogenesiis
. …….. cells have central role in the immune system affecting many other cellular functions
Initial infection causes …… to LN and immune response involving antibodies and ……….. lymphs
steady state but virus still replicates in T cells up to 10^9 virions
T helper cells have central role in the immune system affecting many other cellular functions.
Initial infection causes dissemination to LN and immune response involving antibodies and cytotoxic lymphs.
Steady state but virus still replicates in T cells, up to 109 virions daily.
HIV Pathogenesis
HIV causes persistent infection and destroys large number of …….
Immune system replaces them but eventually overcome
Infected cell life span….. days
HIV ……. immune clearace , also alters its antigenicity and prevents resolution
Progression to clinical AIDs may take ten years or more
HIV causes persistent infection and destroys large numbers of lymphocytes.
Immune system replaces them but eventually is overcome.
Infected cell life span 2.2 days
HIV evades immune clearance, also alters its antigenicity and prevents resolution.
Progression to clinical AIDs may take ten years or more.
Progression to AIDS
Eventually the virus destroys the …. llymphs to an extent where they cannot keep pace,
- Viral load increases and clinical …. appear
Rise in …… ……. infections., and neoplasms
Aldo cause neurological abnormalities
- Dementia - after infection of ….. cells and ……..
Eventually the virus destroys the CD4 lymphs to an extent where they cannot keep pace,
Viral load increases and clinical symptoms appear.
Rise in opportunistic intracellular infections, and neoplasms
Also cause neurological abnormalities
Dementia - after infection of microglial cells and macrophages
HIV clinical sydromes
AIDS related diseases include:
- Opportunistic infection, cancers and CNS disease
Recent research has alterd the management of HIV pos patients
Used to be assessed of … counts
Now assessment of viral load is the most important indicator of infection
AIDS related diseases include :
Opportunistic infection, cancers and CNS disease.
Recent research has altered the management of HIV positive patients.
Used to be assessed on CD4 counts.
Now assessment of viral load is the most important indicator of infection.
Treatment strategies
Measurement of viral load as soon as diagnosis of HIV positivity is made
Treatment strategy callled ……
- Highly….., ……. therapy
Start treatment with combination therapy
- A ……. analogue …… …………. ……….
e. g. AZT (zidovudine) lamivudine
Non nucleoside RTT e.g. nevirapine
Measurement of viral load as soon as diagnosis of HIV positivity is made.
Treatment strategy called HAART
Highly active, antiretroviral therapy.
Start treatment with combination therapy:
A Nucleoside analogue reverse transcriptase inhibitor, e.g. AZT (zidovudine) Lamivudine.
Non nucleoside RTI e.g. nevirapine
Treatment Strategies
Protease inhibitor
- Saquinavir, ritonavir, indinavir.
Viral load should fall within 2-3 ……
If viral load rises, treatment combination can be changed easily
Treatment must be continuous, but dramatic reduction of viral loads have been achieved
Protease inhibitor
Saquinavir, ritonavir, indinavir.
Viral load should fall within 2-3 weeks.
If viral load rises, treatment combination can be changed easily.
Treatment must be continuous, but dramatic reduction of viral loads have been achieved.