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60 Cards in this Set

  • Front
  • Back
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
Shape of HIV-1 core
HIV is easily inactivated by...
Other harsh conditions
Routes of HIV-1 transmission (4)
Mother --> fetus
Breast feeding
Three genes found in all retroviruses
Proteins that GAG encodes

NC - nucleocapsid
CA - capside
MA - matrix
Proteins that POL encodes

RT - reverse transcriptase
PR - protease
IN - integrase
Proteins that ENV encodes
Viral surface glycoproteins
Viral surface glycoprotein responsible for binding
Viral glycoprotein that is bound to each gp120
Most common HIV co-receptors
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
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 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
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
Viral infectivity factor

Necessary for cellular binding factors
Viral protein "r"

Necessary for nuclear export
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?

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
Perhaps because immune evasion is more important early on
What is more abundantly expressed on CD4 cells?


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

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