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74 Cards in this Set
- Front
- Back
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Describe the initial infection stages of HIV
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acute, short viremia 4-8 weeks after infection
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Describe progression of HIV
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remains in the system for about a decade, slowly erodes the immune system
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What is the cause of death in HIV patients?
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opportunisitc disease (pneumonia)
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What is the target cell for HIV?
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CD4 t cells (helper cells, T4 lymphocytes)
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What is the role of T4 lymphocytes in the health individual?
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regulate immune system by controlling proliferation and maturation of beta lymphocytes, natural killers, macrophages, T lymphocytes, and monocytes
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How does HIV attack the T4 lymphocytes?
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gp120 connects to CD4 and chemokine receptor
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What is gp120?
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the surface glycoprotein of HIV that is 120 kDa in length (gp120)
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What is CD4?
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the surface protein on T4 lymphocytes that gp120 binds to
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what is gp41?
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the protein within HIV envelope which is exposed after gp120 binding to CD4. gp41 wiggles into the target cell and allows for transmission
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What is a provirus and how is it formed?
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a provirus is the DNA form of the virus which attacked the cell. In this instance, gp41 allowed the RNA of HIV into the target cell where it was converted to DNA and incorporated into the hosts genome
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What triggers activation of viral genome?
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Y4 cell immune activation triggers transcription and synthesis of the viral genome
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Describe the lysis of T cells in HIV
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When the replicated virus leaves the host cell, they clean up after themselves and lyse the cell
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What is a syncytium?
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a multi-nucleated mass (conglomeration of cells)
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How does HIV form a syncytium?
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gp120 becomes embedded into the host membrane, as a result, it can connect to other cells as well leading to syncytium formation
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Which strains of HIV progress more rapidly, syncytium or non-syncytium forming?
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syncytium forming strains
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What is the difference between CCR5 receptor and CXCR4 receptor?
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CCR5 is M-tropic and CXCR4 is t-tropic, CXCR4 is more destructive
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Describe the immune capabilities of T-cells after HIV infection
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T-cells can destroy cells displaying the viral protections as well as cells with gp120 on their surface (coinfected)
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Describe the RNA composition of the HIV virus
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Consists of 2 strands of RNA which contains all the necessary components (structural, regulatory, and enzymatic proteins)
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Describe the size of the HIV genome
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relatively small, 9749 nucleotides
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Describe the envelope proteins of HIV
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consists of a precursor protein of 160kDa long, which splits into 2 subunits forming gp120 and gp41
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Describe inner membrane protein p17
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18kDa long and attached via acylation to the inner membrane of the HIV envelope. Plays a role in directing RNA, as well as transcription of the virus itself
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Name the core proteins of HIV and their function
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p24, p7, p9 are structural proteins of HIV forming a bullet shaped "nucleocapsid"
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Name 3 enzymes associated with HIV
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protease, integrase, reverse transcriptase
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Describe the reverse transcriptase enzyme of HIV
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consists of DNA polymerase and has Rnase H activity
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Describe the function of integrase of HIV
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plays a role of "integrating" the viral genome into the host cell DNA
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What is the function of protease in HIV?
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to cut the necessary proteins out of a long polypeptide (integral part of the maturation process)
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Describe the lipids in the HIV envelope
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same lipids that are in the T4 membrane
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Describe the transcription process of HIV
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Resting CD4 T-cells contain the non-integrated provirus. Once cell is activated, provirus is integrated and transcription can begin
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What are precursor proteins and how do they fit in to the host cell?
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two large proteins which are fatty acid acylated and inserted into host cell membrane
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Describe the main location within the body that HIV is located
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primarily within the lymphoid organs, small amount in the blood
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Why is HIV complex despite having such a small genome?
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numerous splice sites which can create regulatory or functional proteins
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Name the 3 structural proteins of HIV
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GAG, POL, ENV
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What is the role of GAG in HIV
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structural protein responsible for coding for the core proteins
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What is the role of POL in HIV?
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structural proteins coding for HIV enzymes
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What is the role of ENV in HIV?
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structural protein coding for envelope proteins
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Name 3 regulatory genes of HIV
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REV, NEF, TAT
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What is the role of TAT in HIV?
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stimulates viral protein replication as well as inhibits uninfected T-cell proliferation
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How does TAT perform its function in HIV?
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TAT binds to TAR (a region at the 5' end of HIV) which enhances binding and activation
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What is the role of REV in HIV?
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REV regulates the amount of structural and regulatory proteins being made. REV can also regulate the expression of REV
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What is the mechanism of action of REV?
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post-transcriptional: it binds to splice sites and prevents splicing when proteins are not needed, but removes itself from splice sites when those proteins are needed
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What is the role of NEF in HIV?
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First thought to be a negative effector, now is known to regulate protein transduction allowing for long-term survival of the infected cell by downregulating the CD4 receptor to prevent superinfection
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Location of NEF within the cell?
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located in the cytosol, NOT the nucleus like other proteins
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What is superinfection and what is the result in HIV?
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superinfection is the process by which more provirus is inserted into a cell that has already been infected. This is toxic
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Describe the genetic variability of HIV
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genome has been determined many times, different clades have been identified to have up to 10% difference
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Name 2 reasons HIV is highly mutable
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1) viral DNA polymerase lacks error correcting features
2) cellular RNA polymerase lacks error correcting capacity |
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Describe non-lethal mutations of HIV
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mutations that occur within the regions of the genome which have little or no function
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How does mutation rate affect HIV treatments?
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drug resistant variants arise rapidly in order to circumvent the drug targetting the virus
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Name 5 potential targets in treating HIV
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1) viral fusion
2) Reverse transcriptase 3) Protease inhibitors 4) TAT antagonists 5) Integration |
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What is the current problem with viral fusion method of HIV treatment?
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efficacy
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What is the current problem with treating HIV with reverse transcriptase inhibitors?
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quickly evolve into drug resistant forms
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What is the target of AZT and what are the potential side effects?
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targets reverse transcriptase, potentially causes bone marrow toxicity
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What is the target of ddI and ddC and what are the potential side effects?
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targets reverse transcriptase, can lead to pancreatitis or peripheral neuropathy
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Name 2 antiprotease drugs for HIV
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sasquinavir, ritonavir
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What do Sasquinavir and Ritonavir target
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viral protease
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What results have been seen in HIV patients treated with AZT?
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increases life up to 1 year
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Describe the mechanism of action of AZT
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reverse transcriptase recognizes AZT as thymine and incorporates it into the DNA strand, however since it does not contain a 3' -OH group, nothing else can be added and synthesis comes to a halt
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What side effects are associated with AZT?
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mechanism of action is the same in non-HIV cells (bone marrow) to a lesser extent creating bone marrow toxicity
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How do HIV virus fusion inhibitors act?
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function to block action of gp120
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What is Sirna and how does it work in HIV patients?
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stands for small interfering RNA, strand of oligonucleotides which is complimentary to a section of viral RNA. Once Sirna binds to viral RNA, it activates nucleases which degrade virus
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Name the receptor that keeps some people "immune" to HIV and how does it work?
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CXCR4 is a receptor to binds chemokines and attracts immune cells (which are further attacked by the virus) being CXCR4 mutated means cells cannot become infected
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What do protease inhibitors do in HIV patients?
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they bind to the virus and prevent splicing into active genes
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What is HAART?
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combination HIV therapy utilizing AZT, dd1, and saquinavir.
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Why can't protease inhibitors alone work on HIV patients?
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Because resistance develops rapidly
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What is the problem with HAART?
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expensive and tough (20 pills a day)
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What is the only treatment which has been shown to dramatically increase the lifespan of HIV patients?
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HAART
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Name some reasons an HIV vaccine would be difficult
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1) would need to be potent enough to elicit a response without doing serious damage
2) variability would be tough to create antibodies 3) lack of animal model 4) latent cells cannot be attacked |
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Why does inactive HIV not make for a good vaccine?
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low antigenicity
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Describe how gp120 antibodies work
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Anitbodies bind to loop or pit and prevent binding and/or transmission or viral genome
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Describe the problems encountered with gp120 antibodies
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Binding site on gp120 are well masked by sugars
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What is the problem with utilizing protein subunit vaccines?
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they do not adequately stimulate the cytotoxic lymphocyte response
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What must occur for an adequate defense against HIV in terms of vaccination?
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strong CTL responses and and strong antibody responses
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What were the results of injecting a viral vector CTL vaccine into monkeys?
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Worked at first, mutant strains appeared at 25 weeks
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Where is immune protection needed in HIV?
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sites of viral entry, mucosal surfaces
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Describe the lifespan and progress of HIV
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infects cells, as the cells try to clean up infection, some virus escapes detection and replicates like crazy. Eventually this game of cat and mouse leads to complete erosion of the immune system
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