Najeeb HIV Flashcards
HIV-Related severe impairment of the immune system clinically translates to
Opportunistic Infections
Secondary Neoplasms
Neurological Dysfunction
What type of virus is HIV?
RNA Retrovirus
In the biological world, where is most genetic information normally housed?
DNA (Not true for HIV)
Normal pathway for expressing genetic information
DNA is transcribed to RNA
RNA is translated to Protein
Protein is either Structural or Functional
Pathway for expressing HIV’s genetic information
RNA is reverse-transcribed to DNA
DNA is transcribed to mRNA and Genomic RNA
mRNA is translated into protein
Protein packages the Genomic RNA into a new virus
What helps HIV RNA turn into DNA?
Reverse Transcriptase
The virus carries its own native form, not using the host’s Reverse Transcriptase
HIV Viral Structure (Outside to Inside)
Lipid Bilayer (Envelope) Matrix Proteins (to stabilize envelope protein) Protein (Capsid) 2 identical (not complimentary) copies of RNA
Where does HIV get its envelope?
Host cell plasma membrane
gp41
Transmembrane docking protein in the virus envelope.
Starts as a pedestal for gp120 to sit on (forming gp160), when seeking out a CD4+ cell.
Once gp120 has interacted with CD4 and the appropriate co-receptor, gp41 serves as a fusion molecule, connecting the viral envelope with the host plasma membrane.
Ultimately a fusion molecule.
gp120
Protein that binds to gp41 on virus envelope and likes to interact with CD4 on host cell.
Together with gp41, they form gp160
What type of cell does gp160 like to attach to?
CD4+
CD4+ Cells
T-Helper Cells Monocytes Macrophages Microglia Langerhans Cells Follicular Dendritic Cells
Macrophages in the CNS
Microglia (Also CD4+)
Langerhans Cells
Dendritic cells under the skin (CD4+)
Follicular Dendritic Cells
Dendritic cells in the follicles of lymph nodes
Primary Attachment
gp120 (sitting atop gp41 on the virus envelope) interacts with CD4
CCR5
Chemokine Receptor
Present on Macrophages, serves as a coreceptor for gp120’s new active sites (when activated by CD4)
CXCR4
Chemokine Receptor
Present on Helper T Cells, serves as a coreceptor for gp120’s new active sites (when activated by CD4)
When HIV first enters the body naturally, what is its favorite attachment coreceptor with CD4?
CCR5 (Macrophages)
After several generations of replication, it gains the ability to interact with CXCR4 (Helper T Cells).
What makes someone an elite controller?
Homozygous mutation in CCR5
Northern europeans
A heterozygous mutation just has slow replication of virus.
CCR5 Antagonist
Maraviroc
Inhibits attachment
Why can’t we make a vaccine for HIV yet?
Genetic Variation
gp120 keeps mutating different antigens in its “hypervariable region,” so our antibodies can’t recognize it
What part of HIV does your body make antibodies against?
gp120
These antibodies neutralize the virus.
But then gp120 mutates, and the Ab doesn’t work.
We make new antibodies to the new gp120.
gp41 Inhibitor
Enfuvirtide
Inhibits fusion
Envelope Proteins
gp41
gp120
Gene expressing envelope proteins
ENV gene
Expresses gp41 & gp120
p17
Matrix proteins
Inside envelope, stabilizes gp41 & gp120
Shape of HIV Capsid
Icosahedral
p24
Capsid Protein
What good do p24 Ab do?
Nothing! They can’t reach their antigen because it’s always within cells or the viral envelope
p24 Ab is detectable after a few weeks, and may be followed up by ELISA or Western Blot
p24 Ag
Serological marker of infection, protein from the capsid
What kind of RNA is contained in HIV?
Positive Sense
Dimerized identical copies
What kind of enzymes are contained in HIV?
Reverse Transcriptase (to generate DNA) Integrase (to integrate DNA into host genome) Protease (to cleave proteins into appropriate functional subunits)
Most Common HIV Virus
HIV-1
Global
Least Common HIV Virus
HIV-2
Most common in West Africa
P7
Nucleocapsid protein in HIV
Secondary Attachment
gp120 undergoes a conformational change, exposing 2 more active sites that interact with CCR5 (Macrophages) or CXCR4 (Helper T Cells) on host
Domains of Reverse Transcriptase
RNA-Dependent DNA Polymerase (makes complimentary DNA strand)
RNAase H (destroys template RNA strand)
Mechanism of NRTIs
Nucleotide/Nucleoside analog gets inserted in the process of reverse transcription, but does non contain a hydroxyl tail, so nascent chain can not continue, and is truncated.
NRTIs
Tenofovir Emtricitabine Lamivudine Zidovidune Didenosine Abacavir Entecavir
Mechanism of NNRTIs
Binds to RNA-Dependent DNA Polymerase domain of Reverse Transcriptase, and prevents reverse transcription from taking place
NNRTIs
Efavirenz
Nevirapine
Rilpivirine
Integrase Inhibitors
Raltegravir
Dolutegravir
Elvitegravir
Protease inhibitors
Ritonavir
Lopinavir
Atazanavir
Darunavir
