BIOL243 - L17 End of L16 and HIV

  • Created by: Katherine
  • Created on: 29-04-17 14:25
Which type of herpes is oral?
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Which type of herpes is genital?
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What type of virus is herpes?
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Where is herpes found?
Latent infection in neural ganglia
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What does the herpes virus do?
Blocks MHC class I presentation of antigens - evades cytotoxic T cell recognition
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What is the main antiviral drug?
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What is Acyclovir?
It is a treatment for HSV,
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How does Acyclovir work?
It gets itself incorporated into viral DNA. The Acycloguanosine minic the viral dGTP and is incorporated into new DNA by viral DNA polymerase, but blocks further DNA synthesis. Prevents outbreaks, but doesn't eliminated virus
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What is HIV?
A retrovirus in the lentivirus family Type VI diploid ssRNA)
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What are the two major types of HIV?
HIV I - Causes AIDS, HIV2 - less common, causes a slow developing immune deficiency syndrome. Closely related to simian immunodeficiency virus (SIV) from monkeys and chimps
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How did HIV arise?
Closely related to simian immunodeficiency virus (SIV) from monkeys and chimps - HIV probably arose around 100-130 years ago as a variant of a chimpanzee SIV in central Africa
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What is AZT?
First antiviral developed against HIV. It is a reversse transcriptase (RT) inhibitor. It is a nucleoside analogue so it works on the same principles as Acyclovir.
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How does AZT work?
Phosphorylated in vivo (to AZT triphosphate) and then acts as a chain elongation terminator: limits replication. Binds preferentially to viral RT rather than host DNA polymerases: targets infected cells.
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How many people have died to HIV?
>40 (10^6)
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How many people have died to influenza pandemic?
20 - 40 (10^6)
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How many people died to the black death?
20 - 25 (10^6)
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What is the earliest sign of HIV?
1977 - Kaposi's Sarcoma cases start to appear in young healthy gay men in the USA, 1980 Cryptococcus pneumonia increases in Congo, 4 deaths in USA,
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When did CDC report 285 gases of GRID?
1982 - 285 cases of GRID in 17 US states
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Who are the 4Hs who got HIV?
Homosexuals, Haemophiliacs, Heroin addicts and Haitians
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In 1978, where was HIV found?
New York
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Who was blamed for the AIDs epidemic?
Gaetan Dugas
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Where do they believe HIV started?
From Africa, to the Caribbean, through out the Americas to Europe.
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In Africa there was a 5th H, what?
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Why don't we think that Dugas was patients 0 anymore?
When we do phylogenetics and look at the releationships between HIV samples that have been collected, The common ancestor of America is 1969, too early for Dugas
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What is the structure of HIV?
ssRNA, integrase, gp120,gp41, internal coat, Matrix antigen, tRNA, Capsid, reverse transcriptase, protease, envelope
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What is the genome of HIV?
Typical of all retroviruses. Bordered by LTR (long terminal repeats), Provirus approx 9.8kb
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Which genes are immediately apparent in HIV?
gag (capsid protein), pol (replication enzyme) and env (envelope glycoproteins).
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What are the other genes in HIV?
tat & rev (regulatory genes) nef, viv, vpu and vpr (several non essential genes)
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How does HIV 1 replication occur?
Attachment & entry, uncoating, DNA synthesis, integration and latency, synthesis, assembly and budding, maturation.
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What is the process of attachement and entry
HIV binds to CD4 receptors. The viral gp120 and 41 are bound to cd4 receptors and the vesicle fuses with the membrane. The capsid is released into the
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What is the uncoating stage of HIV replication
The capsid gets uncoated, and the viral genome leaves.
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What is the DNA synthesis stage of HIV replication
The virus gets to work straight away, making double stranded DNA from it's genome. dsDNA isn't vulnerable to Dicer (gene silencer) and it is integrated into the nucleus.
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What is the integration and latency stage of HIV replication
Once it's integrated into the host genome, it starts to be transcribed and translated. The virus coats the outside fo the cell with GP120 and
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What is the asembly and budding stage of HIV replication
Some of the mRNA goes into made genome RNA which is assembled and makes the viral capsid.
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What is the maturation stage of HIV replication
Final maturation occurs after the HIV has been released from the cell.
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What is the primary receptor that HIV binds to?
CD4, it is bound by the HIV gp120 protein.
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What is the CXCR4 receptor?
It is part of the innate immune system but is hijacked. It's a second receptor needed
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How does the HIV gain attachment and entry?
The CD4 will interact with the CXCR4 receptor, allowing the gp41 protein to open up the visicle of the virus and fuse it with the cell.
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How are some people resistant to HIV?
They have an abnormal CXCR4 receptor meaning it doesn't bind to the pg1201 of the virus
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How does reverse transcription occur?
Using a TRNA primer and we made a ssRNA into dsdna which is integrated into the host cell
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Which part of the HIV is recognised by AZT?
It interferes with the synthesis of dsRNA
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What happens in early synthesis of the virus?
mRNA expressed from provirus encoding regulatory proteins (e.g Tat, Rev, Nef) Requires multiple mRNA splice forms
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What do the regulatory proteins do?
Promote high level expression of structural proteins in late phase
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What happens in the late phase of synthesis oF mRNA?
Transcription of sinlge and unspliced mRNAs, as well as genomic RNA. Structural proteisn expressed as large polyproteins.
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WHat are the structural proteins in HIV?
p55 (GAG) precursor for capsid proteins, Gag-Pro-Pol - precursosr for RT, protease, integrase etc, GP160 - precursor for gp120 and gp41 envelope proteins. Cleaved by host protease in Golgi on way to plasma membrane (PM)
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What is the pathogenesis of HIV?
Primary infection, antibody response, clinical latency, antibody population drops, virus replication increases, AIDS
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What are the features of primary infection?
Burst of virus replication. Flu like symptoms or aymptomatic.
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What are the features of antibody response?
Virion count drops, no symptoms but battle between virus and T cells
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What are the features of clinical latency?
Integrated viruses continue to replicate, mutation and selection for resistant virus strains, slow fall in T cell population
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What are the feautes of AIDS?
Suppression of immune response leads to susceptibility to infection. Common causes of death = tuberculosis, pneumonia, thrush, herpes
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Looking at a chart showing the progress of the HIV, what
Sharp increase in p24 antigen after acute infection. This goes down during chronic lympphadenopathy. CD4 T cell count goes down with cchronic lymphadenopathy, while pg120 goes up. By the end, only p24 is risen when there is systemic immune deficieny
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What happens as the CD4 count drops?
Opportunistic infection rises. Loss of immune competence enables normally benign opportunistic parasites - virusesm fungi and protozoa to cause infection.
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