Retrovirus Flashcards
(32 cards)
What are retroviruses
viruses that go from rna-dna-rna?
are retrovirus +or- amd are they ss or diploid
+ and diploid
which call are retrovirus in ba;timore
6
what ais the hallmark of retrpviruses
is their replicative strategy, which includes reverse transcription of the viral RNA into linear dsDNA, which is the
reverse of the usual flow of genetic information
true or false: groups 1-5 in retrovirus are non oncogenic
false they are
what os the organization of the retroviral genome
-gag: directs the synthesis of structural proteins such as matrix, capsid and nucleoprotein
-pol: contains the information for the viral enzymes such as the RT and the integrases
-env: derived the surface transmembrane components such as the viral envelope glycoproteins
what are the 2 main categories of retroviruses
-simple and complex
what is in simple retrovirus
gag
pol
env
what is in complex retrovirus
gag
pol
env
auxilary and regulatory proteins
does hiv have glycoproteins
yeah
retrovira; virion struicture
-Matrix (MA/p17) lines the inner surface of the viral envelope linking it to the viral core. MA also plays
important roles in transport and binding of Gag to the plasma membrane during virion assembly
-= Capsid (CA/p24) monomers dimerize to form the capsid core, which surrounds the viral genome in the
mature virus
-= Nucleocapsid (NC/p7) monomers are structurally associated to the two copies of retroviral ssRNA, and
package them tightly into the viral core
what is the ma,e opf the p that makes up the hiv capsid
p24
retroviral virion structure: virally encoded enzymes
-reverse transcriptase (RT) is a RNA-
dependent DNA polymerase.
= integrase (IN) is an enzyme that enables viral genomic
material to be integrated within the DNA of the cell.
- some retroviruses express proteases which are enzymes that cleave proteins. Although many
eukaryotes express their own proteases, viruses tend to encode their own which are specific to a restricted
set of substrates, e.g. HIV protease cleaves Gag into the components MA, CA, and NC in the mature virion
true or false: hiv is kinda like transposons
true
true or false: HIV only infects humans
false it infects monkeys and cats
HIV Env codes for two glycoproteins
gp120 (extracellular surface)
gp41 (trans-membrane)
-The make-up of envelope glycoproteins depend on the retrovirus; it determines the tissue
and cell tropism of the virus, as this is what binds to cell-surface receptors.
Detailed Steps of the Retrovirus Replication Cycle
- Retroviruses enter the host cell through the attachment of their surface glycoproteins to specific plasma membrane receptors.
- This leads to the fusion of virus and cell membranes and expulsion of the viral core into the cytoplasm.
- In the cytoplasm, the viral RNA (still within the viral core) is transcribed into DNA by the enzyme reverse transcriptase.
- The virus-derived dsDNA is translocated to the nucleus, where it is integrated into the host chromosomal DNA with the aid of
the viral enzyme integrase, to form a stable provirus (i.e integrated HIV dsDNA). - Transcription of the provirus results in spliced and unspliced mRNAs (producing various viral products), as well as full-length
progeny viral (v)RNA genomes (to be encapsidated in the mature virion). - The viral mRNAs are translated by cellular ribosomes.
- The translation products together with the the full-length vRNA traffic to the plasma membrane and assemble into a viral
particle (simplified version). - The viral particle buds from the plasma membrane, acquiring an envelope derived from the cellular plasma membrane.
- Virus maturation is achieved during and following budding by proteolytic cleavage of the viral Gag and Gag/Pol polyproteins into its respective constituents.
how can retrovirus cause cancer
1 –
Viral genes encodes proteins that drive the cell into continuous, uncontrolled proliferation (“foot on the accelerator” model) e.g., src and RSV
2 –
Viral genome can integrate adjacent to cellular proto-oncogenes, and the viral LTR can stimulate aberrant expression of the oncogene (“insertional mutagenesis”), e.g., lymphoid leukemia
and MMTV
3 –
Viral gene encodes a protein that binds and transactivates host cellular genes to
dysregulate the cell cycle and genomic
integrity, e.g., Tax and HTLV-1
what was the first oncogene discovered
src gene in rsv
Retrovirus and insertional mutagenesis
Some retroviruses like the mouse mammary tumor virus (MMTV) produce tumors by
inserting their genomes into the critical sites near or within a proto-oncogene, which
is then converted into an active oncogene by active transcription of the provirus .
what does HTLV 1 cause
an aggressive form of leukemia calles adult T cell leukemia
what does the gene TAX of HTL1 do?
-The gene Tax of HTLV-1 is responsible
for activating transcription of viral
HTLV-1 proteins from the integrated
provirus.
-However, it also has the capacity to
regulate human genes, generally
those involved in cell cycle regulation
and the maintenance of genomic
integrity.
-Tax is what contributes to the onset
of ATL in HTLV-1-infected individuals
Endogenous retroviruses
-Endogenous retroviruses (ERVs) are genetic elements found ubiquitously in eukaryotic DNA, including humans (HERVs).
-They have the ability to amplify themselves to an RNA intermediate (1) and with the help of intrinsically-encoded RT and integrase enzymes,
copy-paste themselves elsewhere in the
genome, in a random fashion (2)
Retroviruses in the biotech industry
-RT is used to make cDNA from an RNA
template for reverse transcription-PCR
-Lentiviruses used as vectors for targeted gene therapy ex vivo
-lentivirus to send the protein acs9