Block 3 MICRO Exam -- HIV/AIDS (#10)

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HIV infects what cells?: CD4 T Cells
Geographical distribution of HIV-1 vs. HIV-2: HIV-1 -- Worldwide AIDS
HIV-2 -- Limited to West Africa
Which is more pathogenic? HIV-1 or HIV-2: HIV-1
Shape of HIV-1 core: Cone-shaped
HIV is easily inactivated by...: Detergents
Alcohols
Iodine
Bleach
Other harsh conditions
Routes of HIV-1 transmission (4): Sexually
Blood-borne
Mother --> fetus
Breast feeding
Three genes found in all retroviruses: Gag
Pol
Env
Proteins that GAG encodes: STRUCTURAL proteins

NC - nucleocapsid
CA - capside
MA - matrix
Proteins that POL encodes: Viral ENZYMES

RT - reverse transcriptase
PR - protease
IN - integrase
Proteins that ENV encodes: Viral surface glycoproteins
Viral surface glycoprotein responsible for binding: gp120
Viral glycoprotein that is bound to each gp120: gp41
Most common HIV co-receptors: CCR5
CXCR4
Important changes gp41 undergoes upon viral attachment (2): Unfolds, inserting helical domain into target cell
Forms coiled structure that brings virus and cell membranes in contact
T20: HIV-fusion inhibitor

Binds unfolded gp41 formation
Designed to prevent formation of 6-member coiled structure
When/where does HIV reverse transcription begin?: DURING uncoating
In the cytoplasm
Pre-Intergration Complex (PIC): Name for the uncoated core particle
Concomitantly with reverse transcription, transits to nucleus
Where is HIV DNA synthesis completed?: In the nucleus
Cellular transcription factors bind viral promoter in what region?: U3 region of the LTR
Where is the TAR located?: Near the 5' end of all HIV-1 transcripts
What does TAT bind?: Cyclin-T1
Cyclin dependent kinase 9

Tat Activation Response (TAR) region of viral DNA
What is the effect of Tat binding?: Modification of RNA polymerase efficiency
Helps make more FULL-LENGTH HIV-1 transcripts
These two initial viral proteins return to the nucleus: Tat
Rev
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
What does Rev do?: Shuttles HIV-1 RNAs to the cytoplasm for translation
Viral RNA molecules are translated into (3): PR55gag - structural protein precursor
PR160 gag-pol - structural protein/enzyme precursor
gp160 - envelope glycoprotein precursor
Vif: Viral infectivity factor

Necessary for cellular binding factors
Vpr: Viral protein "r"

Necessary for nuclear export
Vpu: Viral protein "u"

Assists in degradation of CD4
Precursor protein that viral proteases is initially incorporated in: PR160 gag-pol
Final maturation step: Condensation of the capsid to form the cone shape
When does the final maturation step occur: Not until the virus is free from the producer (host) cell
What do HIV viruses bud through?: Cytoplasmic membrane
What catalyzes HIV's last maturation step: Viral protease
Acute retroviral syndrome: Flu-like illness that accompanies initial HIV-1 infection
Initial species of HIV-1 to be selected for after transmission: CCR5-tropic species
CD4 count progression after infection: 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
Definition of AIDS: Presence, in HIV-1 infected individual, one of following:

One of a number of opportunistic infections/neoplasms
CD4 count < 200 per microliter
Lifespan of untreated pts. after AIDS diagnosis: On average, ONE YEAR
During long asymptomatic phase of HIV, where is replication most active?: Lymphoid organs
Mechanisms through which HIV-1 kills cells (4): Induction of apoptosis
Formation of syncytia
Disrupting cytokines
Destroying structure of lymphoid organs
What is the most variable HIV-1 protein?: gp120

Has 5 variable regions V1 - V5
V3 region of gp120: 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
Functions of Nef protein: Downregulates CD4 and MHC-1 expression

Interacts with cellular kinases
Enhances viral infectivity
What do early HIV-1 isolates downregulate better? MHC-1 or CD4: MHC-1
Perhaps because immune evasion is more important early on
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
Homozygosity at HLA-1 loci A,B,C is assoc. w/ what?: More rapid progression of disease
Individuals w/ what mutation are more resistant to HIV-1?: CCR5 delta-32

Homozygous -- highly resistant to HIV-1 infection

Heterozygous -- susceptible to infection, BUT, progresses slowly
How long is the replication cycle for HIV-1?: 1.5 days
How often is an error made by reverse transcriptase?: One error in every third genome
When is the co-receptor binding site of HIV-1 exposed?: Only AFTER intiial binding of CD4
HIV-1 gp120 is covered with what that helps it evade immune detection?: Glycosyl groups identical to those on host proteins
Where is the HIV-1 CD4 binding site located?: Hidden in a cleft of gp120

This contributes to succesful immune evasion
What classes of MHC-1 does HIV-1 down-regulate?: A and B
NOT C

NOTE: NK cells recognize class C
How is fas-ligand used by HIV-1?: 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
What HIV-1 subtype predominates in the U.S.?: Subtype B

Remember, clades A-K are referred to as M subtypes
What is higher risk for transmission? Male --> Female OR Female --> Male: Male --> Female

Many CD4 cells line the vagina
How do oral contraceptive affect chances of HIV infection?: They are associated with INCREASED CCR5 expression
Who is more at risk for HIV? Circumcised OR Uncircumcised: Uncircumcised at 2-8x greater risk
When do HIV Ab tests usually become positive?: Approximately 28 days after infection

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