Exam IV: Lecture 14 Flashcards
What is the signature of a retrovirus?
It uses Reverse Transcriptase
The genetic information of retroviruses alternate from what to what?
RNA and DNA
What is a provirus?
A retrovirus in a dsDNA version that is integrated into the host genome
Is the integration of retroviruses required for transcription and replication of the genome?
Yes
Retroviruses are known to cause 2 diseases in humans. What are they?
- AIDS via HIV
2. Adult T-cell leukemia via HTLV-1 infection
What would be a good target for antivirals against retroviruses?
Reverse trancriptase
How can a provirus lead to cancer?
- Disrupt tumor suppressor gene
- Insert in front of an oncogene
- Bring their own v-oncs with them
How long does the insertion of the provirus into the host DNA last? What is the implication of this?
It is permanent
Our genomes are littered with retroviruses that have become inactivated
What are retroposons? What can they do?
Ancient traces of retroviruses found in the genome of eukaryotes that are no longer infectious
They can insert into different parts of the genome
Is the genome of retroviruses haploid or diploid?
Diploid: two copies exist in each capsid
How long is the retroviral genome?
7-10 kb of ssRNA
What is a unique feature about retroviral RNA?
It is capped and polyadenylated
What are the 4 main genes in the retroviral genome?
- gag
- pro
- pol
- env
What is the potential “parent” of HIV?
SIV in Monkeys which causes Simian AIDS
What is a lentivirus?
A virus that is slow to show symptoms and established a lifelong chronic infection
Tropism = macrophages
What does gag do?
Capsid protein, structural, groups specific antigens
What does pol do?
reverse transcriptase; Rnase and integrase
What does pro do?
Protease, required for processing of gag
What does env do?
glycoproteins
Talk me through infection of the cell with retrovirus
virus enter cell > release genome > enters into nuclues > integration into DNA = provirus > transcription etc
How does HIV enter the cell?
gp120 binds to host CD4 > conformation change of gp130 + gp41 > coreceptor reaction with CCR5 (macrophages)/CXCR4(T-cells) + gp41 > virus anchors into the membrane of CD4+ cell > gp41 changes into coiled shape > brings virus and cell membrane together > fusion > entry and uncoating
What is the benefit to be being born without CCR5?
Immune to HIV
What cells does HIV infect? What is the implication of this?
T-cells/Macrophages > AIDS (autoimmune disorder)
Where does reverse transcription occur after infection?
Within a subviral particle in the cytoplasm
Talk me through the process from entry to integration
Entry > reverse trancription in subviral particle = produce dsDNA > dsDNA enters nuclues during mitosis = need actively dividing cell > integrates into host chromosome randomly using integrase
Talk me through reverse transcription
tRNA is packages in the capsid. tRNA contians sequence that is complementary to viral genome > binds to viral genome and serves as primer > reverse transcriptase extend the OH group with DNA nucliotides > RNaseH (H = hybrid) degrades the RNA after the DNA is made > R of 5’ end has homology with the R sequence at the other end so it jumps and starts elongation again»_space; forms cDNA (c = complementary) with repeats on both ends
Is insertion stable or unstable?
It is stable
The retrovirus does not always kill the host cell and can exist as a _____ gene within the host
Mendelian gene
What contains all of the signals required for transcription?
The LTR: includes binding sites, TATAT box
Most signals required for transcription are found in which gene segment?
U3
Transcription of retroviruses always begins where?
The 5’ LTR
The processes RNA transcript is identical to the genome and can be packed into progeny viruses
True
Is the rate of transcription of retrovituses high or low?
Very high (potential target for drugs) Another reason for why it would lead to cancer if integrated in front of a oncogene
What are the 4 reasons retroviruses induce uncontrolled cell growth?
???
Does the DNA of retroviruses contain a stop codon? What is unique about this?
Yes it does
But the virus can skip the stop codon > mRNA with many genes > polyprotein > proteolytic cleavage
What is translational frameshift? How does it happen?
The ribosome reads 3 nucleotides at a time > A RNA pseudoknot (before stop codon) can cause the ribosome to slide back and read with a different 3 reading frame > stop codon is no longer the stop codon > ability to create multiple proteins from one simple genome
The pseudoknot is one specific nucelotide?
How does the virus acquire its envelope?
By budding through the plasma membrane
In HIV, distinct capsids are not seen within the host cell, how can this be explained?
The capsid comes together just before the virus leaves the cell
How is the capsid formed (what 3 proteins are used)? What does it look like?
Formed by the assembly of Gag, Gag-pro, and Gag-pro-pol polyproteins
Spherical structure 100nm in diameter
What is the final step after the capsid is formed that makes the virus particle infectious?
The polyproteins (gag-pro and gag-pro-pol) are cleaved
Why are most transforming retroviruses defective?
They pick up oncogenes by recombination with a host cell which replaces an essential part of the viral genome
What is an example of a disease caused by a v onc?
Erythroblastosis (erbB)
Sarcomas
HIV1 and 2 belong to what family?
Lentivirus family
Infection with HIV induces a vigorous immune response that is unable to clear the virus
True
Why does the lentivirus family contain so many different genes? (3)
Splicing
Framsheifing
Fusion protiens
Complex retrovirus have more complex genomes
True
Which is more pthogenic HIV 1 or 2?
HIV 1 > the main cause for AIDS in most infected persons
Talk me through HIV infection in the clinical sense
Does HIV infect CD4+ Tcells and macrophages > primary infection can be asymptomatic or rash/fever/diarrhea/myalgia/nausea/sore throat > immune response is mounted by CD8+ T cells and B cells > reduces amount of virus > symptoms lessen > disease enters clinical latency > large amounts of virus are made by patient in lymph nodes > steady decline of CD4+ cells > AIDS
What are 2 important functions of CD4+ T cells?
- Activate CTLs
2. Activate B-cells
Ablation of CD4+ cells results in the establishment of opportunistic infections int he host including fungal, bacterial, protozoa, and viral infections
True
How low a count of CD4 cells is required to be “full blown AIDS”
Less than 200
How is HIV/AIDS transmitted?
Blood-borne
Sex
Congenital transmission (blood mixing)
What are quasispecies?
Highly mutated HIV particles that your antibodies can not fight against
What are two unique infections a person with AIDs can get?
- Oral andidiaiases (thrush)
2. Kapozis sarcoma
Is there a vaccine for HIV?
No
What is the best way to prevent HIV?
Practice safe sex
Check all blood to make sure it is safe
What does HAART stand for? What is it?
Highly Active Antiretroviral Therapy
Combination therapy using a multiple inhibitors
What are some of the inhibitors seen in HAART? (4)
- Reverse transciptase inhibitors
- Protease inhibitors
- Integrase inhibitors
- Entry inhibitors
Why do you need HAART to treat HIV/AIDs?
RNA easily mutates to become resistant to the drug so you have to hit it with multiple
What is the hypothetical start to HIV?
Sailor in the UK got SIV from apes in Africa after he killed the primate and had blood-blood contact. It is a relatively new virus
