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30 Cards in this Set
- Front
- Back
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What are the characteristics of the Picornvirus genome and its virion?
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-Linear
-ssRNA (+) -7-8.5 kb -naked (non-enveloped) virus -iscosahedral symmetry |
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How many mRNAs does this virus have?
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-One mRNA: codes for a single polyptn that is cleaved by viral proteases into smaller ptns in the cell
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What are the gene product of this virus?
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-3capsid ptns
-1-3 proteinases -->Cleaves the polyptn encoded by the genome into single fctnal ptns -6-8 Replication ptn: replication more complicated cuz start with RNA. Also replication isnt free floating, its tethered to the mb of the cytoplasm |
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What is VPg?
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small virus-coded ptn unique to picornavirus.
-Covalently attached to 5'end of RNA genome. -Serves as prmer for the viral pol to start replication -prevents viral degradation by acting as a protective cap to the mRNA |
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Whendoes cleavage of the large precursor polypeptide byviral proteinases take place?
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Immediately after translation of the viral polyptn
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What are some examples of Picornaviruses?
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-Enterovirus (Polio)
-Cardiovirus -Rhinovirus |
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What is an acute virus?
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Virus that goes into the cell and can kill it quite rapidly by taking over the cellular machinery and using it to make a lot of virions
-Can spread quickly and cause acute infections -Acute infection are brief but cause a lot of harm |
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What are Chronic viruses?
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-Don't take over host completely(go in and live with the cell)
-They make less progeny and try to hide from the immune system -Usually don't kll the cell and go away over time |
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How does the virus enter the cell?
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-Have structure on capsid (which has 20 triangles) that bind to the receptors on host cells
-Dif viruses use dif receptors, some use more than 1 receptor Tropism: specific infectivity of tissues |
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How is the capsid of a picornavirus formed?
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-Have P1 (polyptn) which is cleaved into VP 1/2/3/4
-VP1/2/3 forms a Protomer (5S) which forms a Pentamer (14S) which assembles to the empty capsid (80S) -The genome is then inserted into it => Provirion (150S) |
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How do you get an infectious virion?
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Cleave VP0 to VP2 + VP4
(Provirion is not infectious cuz you don't want to have infectous viruses in the cell) |
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How does the virus get its RNA into the cell?
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2 ways
1) Endocytosis: virus binds receptor, changes conformation. Induction due to low pH, allows RNA to get out. VPg will make a hole and let the RNA enter the cytoplasm 2) Virus can bind the receptor and VP4 comes off. VP1 changes conformation upon binding and forming a hole thorugh the plasma mb, allowing for RNA to escape |
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What does the genome look like (5' and 3' ends)?
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-5' end: VPg ptn that forms a CAP and is imp for replication
-5' oncoding region: has Internal Ribosomal Entry Site (IRES) which forms a RNA structure that allows non-conventional ribosomal attachment --> imp for translation and replication -3' end: Poly(A) tail imp for rep -->dif from humans cuz the virus codes for the poly-A stretch are in the genome already (not added later). Required as a primer for replication cuz VPg acts as a primer and, covalently bound to 2 U's, will bind to the A's |
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What is the Leader Protein (L) of the polypeptide ptn?
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-A protease
-When ptn is made, cleavage of polyptn into P1, P2 and P3 |
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What are the 2 types of ptns?
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Structural Proteins
-> P1: VP1-VP4 Non-structural ptns: -> P2: (2A,B,C) These ptns requied for replication -> P3: (3A, B, C, D) -3B is VPg -3C is the main protease ans is conserved in all viruses -3D encodes RNA-dep-RNA-POL |
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How can the infection be studied?
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-Look at Rate of Ptn Synthesis
--> use radioactive aa in sol'n and let cells translate ptns. Plot these on Western BLot/x-ray film --> Found that cellular translation is shut off while viral tanslation is still on, so the virus manages to hijack the E of the cells to direct ptn synthesis only towards viral ptns |
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What is different about viral translation of picornavirus, as opposed to mammalian translation?
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-Have long 5' UTR with IRES in the RNA (.: ribosome will bind mRNA internally, instead of at 5' end)
-Many AUG in the non-coding regions that aren't used for initiation of ptn synthesis -2 Types of IRES (Type 1: 6 stem loop; Type 2: 12 stem loop) |
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In tye I IRES, what happens when the PolyRC binds:
1) stem loop 4? 2) Stem loop1? |
1) PolyRC binds stem loop 4, allows ribosome binding and translatio can occur
2) PolyRC binds stem loop 1, inhibits translation and activates replication -also require mammalian ptns |
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What is the initiator sequence for Type I IRES? Type 2?
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Type I: NOT AUG
Type II: AUG |
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Will two viruses of the same type have the same structural homology even though there is no conservation of sequence?
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Yes
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Will a circularized picornavirus without a 5' cap be translated?
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Only if the virus has an IRES can it be translated without a 5' cap
(For normal ss linear RNA. using the IRES and 5' initiation, you have 2 possibilities for translation of ptn) |
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How does the picornavirus shut off host translation?
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1-Use 2A or L protease to cleave off the eiF-4G (which holds ptns of the eIF-4F complex together)
-part with the eIF-4E cap binding ptn falls off so remaining segment can't bind to the cap and regular cell translation can't be initiated (Virus replication only needs fragment of eIF-4G with eIF-4A and an IRES for translation of viral RNAs) 2-Can also use 4E-BP1 to get rid of eIF-4E. deP 4E-BP1 that will bind to eIF-4E and take it away from the 5E complex, preventig translation at the 5' cap (this mech done in ECMV/Poliovirus) |
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What proteases are used to process the poly ptns?
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1) just 3C: does first 3 cleavages to get P1/P2/P3
-Cleaves itself, gets other proteases to do other cleavages, doesn't shut off ptn synthesis 2) 3C and 2A -2A: can cleave itself and host ptn, but can't cleave any other viral ptns 3) 3C, 2A and L? |
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How does the virus become infective?
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Furin (cellular protease) cleaves 1A to 1B as a final step to make the virions infective
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How is the Picornavirus genome replicated?
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-Start with (+)mRNA--> (-) mRNA --> (+) mRNA
-Start with + and make - cuz these - will make more + strands (get amplification) |
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What are the 3 forms Picornavirus can be seen under in an infected cell?
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- ss(+) mRNA
- Replicative intermediate: (-) strand attached to many (+) strands (- being made from +) -Replicative form: Finished product: +/- strand hybrid (many + strands being polymerized off of each of the - strands) |
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Why is VPg imp at the 3' end?
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Acts as a primer cuz its linked to 2 U's (allows repl from 5'-->3')
VPg is on the 5' end of the viral genome, but due to folding, it interacts with the 3' end |
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What is 3D?
What is 3CD imp for? |
-Polymerase
-Starts synthesizing the (-) strand as soon as VPg binds th polyA tail -3CD; imp for replication. Contains a protease (3C) and a polymerase (3D) |
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What is the 3A/3B comlex for?
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Important for attachment to the ER mb for assembly of the virus
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What is PCBP?
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Poly C Binding Ptn
-Regulates translation and replication depending on which hairpin structure it binds to (1 = replication, 4= translation) |
