Term
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Definition
| establish and maintain stable associations with their host = great survival advantage and long term |
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Term
| What unique enzyme makes the virus a "retro virus"? |
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Definition
The Reverse transcriptase!
-->Appears to have the RNaseH as a 2nd function (yet to be confirmed) |
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Term
| Three main retro virus groups |
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Definition
| oncornaviruses, lentiviruses, spumaviruses |
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Term
| What is the integrated cDNA called |
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Definition
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Term
| Retroviruses modify/disrupt almost nothing about the host cell... what implications does that have on the cells ability to counteract virus? |
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Definition
| There practically no ways for the cell to evolve methods of countering the expersion of the viral genes because that would involve changing a function of their own (plus there is no detection anyways) |
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Term
| Retrovirus structure basics |
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Definition
(+) ss RNA (diploid)
Enveloped
Virus capsid (GAG)
Three extremely important enzymes:
-Reverse transcriptase
-Protease
-Integrase |
|
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Term
| Describe the genomic RNA of retroviruses - why is it that way? |
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Definition
It is a capped and polyadenylated mRNA! (~10kb)
This is because the copy was made off of the integrated provirus |
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Term
| All retroviruses have 3 essential genes and untranslated regions.... describe |
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Definition
5'cap: R : U5 : Leader : Gal-pol : int : env : (PPT) : U3 : R : PolA(n)
U=unique region
R=repeated at both ends |
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Term
| Reverse transcription of the RNA into DNA is complex, so learn the key concepts: |
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Definition
Starts at PBS (primer binding site) because DNA polymerases NEED a primer! The combined work of RT and its RNaseH function create a dsDNA out of a ssRNA.
The mix of U3/R/U5 creates the LTR eukaryotic "promoter". |
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Term
| Human T-cell leukemia (HTLV) |
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Definition
| complex retrovirus containing extra genes; tax and rex, that are responsible for stimulating cell division and metabolic effects = growth ==> leads to cancer! |
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Term
|
Definition
Receptor-mediated endocytosis (CD4 + co-receptor)
Partial uncoating and exposure of capsid
RT begins |
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Term
|
Definition
| EX. HIVgp120 binds CD4 and conformation change occurs exposing co-receptor binding domains. Binding of co-receptor causes 2nd confirmation change = contact with host cell membrane and "twist" causing the fusion |
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Term
| oncornavirus entry into nucleus |
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Definition
| Requires cell division (ex HTLV) |
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Term
| Lentivirus entry into nucleus |
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Definition
Does not require cell division to take place because of a unique characteristic that enables cDNA passage into the nucleus (integrase + others)
->the fact that the cDNA can be inserted into non-dividing cells makes them more pathogenic! |
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Term
|
Definition
Long terminal repeat
=both promoter and polyadenylation/stop signal
-can also act as enhancer |
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Term
| Because HIV can infect non-dividing cells it can infect these cells: |
|
Definition
| macrophages, including microglial cells in the brain and can cause neurological disease. |
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Term
| What 6 accessory genes are encoded by HIV |
|
Definition
| vif, vpr, tat, rev, vpu, nef |
|
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Term
| Why can you not block the binding of HIV to CD4 with ABs? |
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Definition
| The binding is occurring in a a site too small for most Ab's to bind or block, furthermore, the secondary binding of the co-receptor is a VERY brief moment and cannot be "tagged" |
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Term
| How can the HIV protect its self against cytidine deamination from APOBEC? |
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Definition
| The vif protein can tag the APOBEC proteins for degradation (ubiqitination) in the cytosol |
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Term
| What does TAT protein do? |
|
Definition
| The mRNA from the provirus (insert cDNA) contains secondary structure and cannot be translated at full force. THe TAT unfolds the RNA and increases the translation 100 fold. |
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Term
|
Definition
| Promote transfer of protein through the cytosolic membrane (can be used for drug import into cells!) |
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Term
|
Definition
| transports vmRNA out of the nucleus and then comes back (NLS). This is a level of control b/c the mRNA's cannot leave the nucleus without this rev, therefore, until rev is made, the mRNA's are not translated. |
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Term
|
Definition
| enhance LTR activity and arrests the cell in G2 phase (this is the best phase for transcription) |
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Term
|
Definition
| downregulates host cell's CD4 expression and MHC-1 to evade immune system. |
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Term
| people who are resistant to AIDS |
|
Definition
| may have a homozygous deletion in their co-receptor such that the HIV cannot undergo the changes necessary to enter the cell! v. late AIDS - heterozygotes = v. delayed AIDS |
|
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Term
| Acute phase infection of HIV |
|
Definition
HIV replicates in high levels in blood and lymphoid organs. A majority of intestinal mucosal CD4 cells are distroyed! (~half the Thelper cells in body!)
-->then into clinical latency |
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Term
|
Definition
This is the stage where the immune system has suppressed the system enough that the viral replication is maintained at a "set point" = low set point means a longer life exp. (before AIDS)
-CD4 cells are still dying and some CD8 cells too
-HIV is becoming selectively more virulent |
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Term
|
Definition
| defined by a CD$ count of less than 200/microliter (normal = 1000/microliter) |
|
|
Term
| How does intracellular defense mechanism APOBEC lead to hypermutaion of the HIV1 genome? |
|
Definition
The C's get deaminated and upon transcription to DNA, the regular G would be replaced with T = hypermutation
-->HIV defense = vif |
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