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60 Cards in this Set
- Front
- Back
HIV infects what cells?
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CD4 T Cells
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Geographical distribution of HIV-1 vs. HIV-2
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HIV-1 -- Worldwide AIDS
HIV-2 -- Limited to West Africa |
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Which is more pathogenic?
HIV-1 or HIV-2 |
HIV-1
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Shape of HIV-1 core
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Cone-shaped
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HIV is easily inactivated by...
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Detergents
Alcohols Iodine Bleach Other harsh conditions |
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Routes of HIV-1 transmission (4)
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Sexually
Blood-borne Mother --> fetus Breast feeding |
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Three genes found in all retroviruses
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Gag
Pol Env |
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Proteins that GAG encodes
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STRUCTURAL proteins
NC - nucleocapsid CA - capside MA - matrix |
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Proteins that POL encodes
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Viral ENZYMES
RT - reverse transcriptase PR - protease IN - integrase |
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Proteins that ENV encodes
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Viral surface glycoproteins
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Viral surface glycoprotein responsible for binding
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gp120
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Viral glycoprotein that is bound to each gp120
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gp41
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Most common HIV co-receptors
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CCR5
CXCR4 |
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Important changes gp41 undergoes upon viral attachment (2)
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Unfolds, inserting helical domain into target cell
Forms coiled structure that brings virus and cell membranes in contact |
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T20
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HIV-fusion inhibitor
Binds unfolded gp41 formation Designed to prevent formation of 6-member coiled structure |
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When/where does HIV reverse transcription begin?
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DURING uncoating
In the cytoplasm |
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Pre-Intergration Complex (PIC)
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Name for the uncoated core particle
Concomitantly with reverse transcription, transits to nucleus |
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Where is HIV DNA synthesis completed?
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In the nucleus
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Cellular transcription factors bind viral promoter in what region?
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U3 region of the LTR
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Where is the TAR located?
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Near the 5' end of all HIV-1 transcripts
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What does TAT bind?
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Cyclin-T1
Cyclin dependent kinase 9 Tat Activation Response (TAR) region of viral DNA |
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What is the effect of Tat binding?
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Modification of RNA polymerase efficiency
Helps make more FULL-LENGTH HIV-1 transcripts |
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These two initial viral proteins return to the nucleus
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Tat
Rev |
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Rev response element (RRE)
Where is it found? |
Region of the HIV-1 RNA
Spliced out of 2kb molecules for Tat, Rev, Nef Found in all other HIV-1 transcripts |
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What does Rev do?
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Shuttles HIV-1 RNAs to the cytoplasm for translation
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Viral RNA molecules are translated into (3)
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PR55gag - structural protein precursor
PR160 gag-pol - structural protein/enzyme precursor gp160 - envelope glycoprotein precursor |
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Vif
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Viral infectivity factor
Necessary for cellular binding factors |
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Vpr
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Viral protein "r"
Necessary for nuclear export |
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Vpu
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Viral protein "u"
Assists in degradation of CD4 |
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Precursor protein that viral proteases is initially incorporated in
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PR160 gag-pol
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Final maturation step
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Condensation of the capsid to form the cone shape
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When does the final maturation step occur
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Not until the virus is free from the producer (host) cell
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What do HIV viruses bud through?
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Cytoplasmic membrane
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What catalyzes HIV's last maturation step
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Viral protease
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Acute retroviral syndrome
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Flu-like illness that accompanies initial HIV-1 infection
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Initial species of HIV-1 to be selected for after transmission
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CCR5-tropic species
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CD4 count progression after infection
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Initially, while viral replication is unopposed, CD4 count drops
Once replicative burst is contained, CD4 count rebounds somewhat Over long-term, CD4 count gradually declines |
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Definition of AIDS
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Presence, in HIV-1 infected individual, one of following:
One of a number of opportunistic infections/neoplasms CD4 count < 200 per microliter |
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Lifespan of untreated pts. after AIDS diagnosis
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On average, ONE YEAR
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During long asymptomatic phase of HIV, where is replication most active?
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Lymphoid organs
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Mechanisms through which HIV-1 kills cells (4)
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Induction of apoptosis
Formation of syncytia Disrupting cytokines Destroying structure of lymphoid organs |
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What is the most variable HIV-1 protein?
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gp120
Has 5 variable regions V1 - V5 |
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V3 region of gp120
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Primary determinant of co-receptor interaction
NOTE: in 1/2 of pts. this eventually evolves to allow CXCR4 tropism NOTE: CXCR4 tropism is assoc. w/ more rapid disease progression |
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Functions of Nef protein
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Downregulates CD4 and MHC-1 expression
Interacts with cellular kinases Enhances viral infectivity |
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What do early HIV-1 isolates downregulate better?
MHC-1 or CD4 |
MHC-1
Perhaps because immune evasion is more important early on |
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What is more abundantly expressed on CD4 cells?
CCR5 or CXCR4 |
CXCR4
HIV-1 eveolves to be tropic to this later in infection Evolution to this is assoc. w/ more rapid progression |
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Homozygosity at HLA-1 loci A,B,C is assoc. w/ what?
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More rapid progression of disease
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Individuals w/ what mutation are more resistant to HIV-1?
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CCR5 delta-32
Homozygous -- highly resistant to HIV-1 infection Heterozygous -- susceptible to infection, BUT, progresses slowly |
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How long is the replication cycle for HIV-1?
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1.5 days
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How often is an error made by reverse transcriptase?
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One error in every third genome
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When is the co-receptor binding site of HIV-1 exposed?
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Only AFTER intiial binding of CD4
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HIV-1 gp120 is covered with what that helps it evade immune detection?
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Glycosyl groups identical to those on host proteins
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Where is the HIV-1 CD4 binding site located?
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Hidden in a cleft of gp120
This contributes to succesful immune evasion |
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What classes of MHC-1 does HIV-1 down-regulate?
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A and B
NOT C NOTE: NK cells recognize class C |
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How is fas-ligand used by HIV-1?
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Expressed on HIV-1 infected cells
Helps evade CTL, since they express Fas Fas-ligand induces apoptosis when engaged by Fas-ligand SO, HIV-1 infected cells kill CTL before they can act |
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What HIV-1 subtype predominates in the U.S.?
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Subtype B
Remember, clades A-K are referred to as M subtypes |
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What is higher risk for transmission?
Male --> Female OR Female --> Male |
Male --> Female
Many CD4 cells line the vagina |
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How do oral contraceptive affect chances of HIV infection?
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They are associated with INCREASED CCR5 expression
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Who is more at risk for HIV?
Circumcised OR Uncircumcised |
Uncircumcised at 2-8x greater risk
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When do HIV Ab tests usually become positive?
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Approximately 28 days after infection
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