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89 Cards in this Set
- Front
- Back
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In what form is the genome of Picornaviruses?
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linear (+)ssRNA
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How big the the genome of Picornaviruses?
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7-8.5kb
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How many capsid proteins do Picornaviruses have?
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4
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How many proteinases are made in Picornaviruses?
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1-3
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How many proteins in Picornaviruses are responsible for replication?
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6-8
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What protein is linked to the 5' end of the genome?
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VPg
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How many proteins are originally transcribed?
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a single polyprotein which will be cleaved co-translationally
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What kind of genome do Picornaviruses have?
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(+) ssRNA
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Where does Picornavirus replication take place in the cell?
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tethered to ER membrane
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Name some genera of the Picornavirus family:
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-Enterovirus (polio, coxsackie...)
-Rhinovirus -Cardiovirus (ECMV) -Apthovirum (FMDV) -Hepatovirus (Hepatitus A) -Parechoviruses |
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Which Picornaviruses are acute?
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ECMV (cardiovirus)
FMDV (aphthovirus) |
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Which Picornaviruses are chronic?
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rhinovirus
hepatovirus (hepatitis A) |
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What kind of receptors are used by Picornaviruses?
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-immunoglobulins
-compliment proteins -integrins -GAGs -carbohydrate |
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What is a receptor used by poliovirus?
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Pvr/CD155
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What is a receptor used by Coxsackie virus?
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Car
many others |
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What is a receptor used by Rhinovirus?
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Icam-I
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FMDV
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heparan sulfate
vitronectin receptor (alphaVbeta2) |
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Which proteins make up a face of the icosahedral capsid of picornaviruses?
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VP1
VP2 VP3 VP4 |
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What is required to make a virion particle active?
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cleavage of VP0 to VP2 and VP4 by furin (cellular protease)
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What are the 2 methods of entry of Picornaviruses?
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1. endocytosis
2. uncoating |
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In endocytosis, which pH is required for uncoating?
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pH = 2-3
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Which capsid protein makes up a pore for uncoating?
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VP1
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Which protein acts as a primer and enters the VP1 pore first during uncoating?
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VPg
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Which element in the 5' portion of the genome is important for binding of the replicase complex?
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IRES (600-1200NTs)
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What are the structural proteins of the genome?
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L
VP4 VP2 VP3 VP1 -------->initially = P1 |
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What three proteases are there in the genome?
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3C (conserved in all Picornaviruses)
2A L (not in Polio) |
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Which protein is the RNA-dep.-RNA-pol.?
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3D
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Which NS protein serves as a replication primer?
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VPg
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Which part of the genome is required for export from the cellular nucleus?
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poly(A) tail
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At what time after infection do we see begining of viral protein synthesis?
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3 hours
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What are the two types of IRES's?
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A - 6 loops
B - 12 loops |
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How were the structures of IRES's predicted?
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RNase digestion
computer prediction |
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Where is polyC bound during replication? during transcription?
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loop I - replication
loop IV - translation |
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Which region is highly conserved?
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pyrimidine-rich region
initiator AUG |
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What is conserved between different IRES's?
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structure
NOT sequence!!! |
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Which cellular protein binds to the cap?
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eIF-4E
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Which cellular protein is a scaffold (brings RNA and cap together)?
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eIF-4G
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Which cellular protein in RNA helicase?
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eIF-4A
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Which ribosome subunit is brought to the RNA by the pre-initiation complex?
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40S (small subunit)
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What is brought to the initiation complex when the 40S subunit when it find the AUG sequence?
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60S (large subunit)
met-tRNA binds |
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Which proteases cleave eIF-4G to inhibit cellular protein synthesis?
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2A/L
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Which viruses cleave eIF-4G?
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EMCV
FMDV polio ----->acute infections |
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What is another method to inhibit cellular translation?
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dephosphorylation of 4E-BP1 (binds 4E)
-polio -EMCV |
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Which viruses have L?
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cardio (ECMV)
aphtho (FMDV) |
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Which protease is self-cleaving?
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2A
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What is an advantage of replication from (+) ssRNA --> (-) ssRNA --> (+) ssRNA?
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amplification during multistrand replicative intermediate
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Which three genera make up the Flaviviridae?
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Flaviviruses
Pestiviruses Hepaciviruses |
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What treatment is currently available for Hepatitis C?
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interferon + ribavirin
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What are disadvantages or this therapy?
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-expensive (40000$/year)
-limitted efficacy (20-40%) -side-effects: flu-like symptoms!! |
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What are the structural viruses of HCV?
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core
glycoproteins - E1, E2 |
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What are the 2 proteases of HCV?
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NS2 - cleaves cysteine (like 2A)
NS3 - cleaves serine (like 3C) |
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Which protein is the RNA-dep.-RNA-pol. in HCV?
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NS5B
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Which protein is also a helicase?
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NS3
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Which is the NS3 cofactor?
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NS4
release and binds to NS3 to become part of the protease |
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Does the HCV genome need a primer?
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No! (nothing like VPg...)
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Does the HCV genome have a poly(A) tail?
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No! (but the 3' region is conserved)
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What are the receptors for HCV?
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unknown (3 or 4)
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Which cell culture can be used to culture HCV?
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Huh-7 cells (hepatoma cell line)
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What are three drug targets for HCV?
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-protease (non-cellular)
-polymerase -helicase |
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What was the first target explore for HCV?
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NS3 serine protease
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What is a non-random method of finding drugs to target specific enzymes called?
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rational drug design
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Why was Compound A rejected?
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cardiovascular side effects
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What are some potential drug targets for HCV?
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receptors
p7 (ion channel) NS3 helicase NS5 polymerase membrane-association NS2, NS3 protease |
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What is the size of Flaviviruses?
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50nm
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What form is the capsid of Flaviviruses in?
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icosahedral
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What sort of symmetry does the envelope have?
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icosahedral
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What form is the genome of Flaviviruses?
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(+) ssRNA
10 - 12.3Kb |
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Which genera of Flaviruses have a 5' cap?
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Flavivirus genus (NOT pesti/HCV)
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Where do these viruses replicate?
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cytoplasm
need own capping enzymes |
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What are the envelope proteins of Flaviviruses?
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M and E
prM hides E until it is cleaved by Furin (host protease) |
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How are most Flaviviruses transmitted?
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by insect bites
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Which genera have IRES's?
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pesti
Hepaci |
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Is Flavivirus uncoating pH-dependent?
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yes!!
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What is the size of Coronaviruses?
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120-160nm
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What is the form of the Coronavirus nucleocapsid?
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helical
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What form can the core shell of the Coronavirus be in?:
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icosahedral
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What is the form of the Coronavirus genome?
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(+) ssRNA
27-32kb (BIG) 5' cap 3' poly(A) tail |
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How many genes/proteins are coded for by the Coronavirus genome?
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6-9 genes
> 20 proteins produced by cleavage |
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Describe the inital replicase genes transcribed:
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2 ORFs connected by frameshift (polyprotein)
cleaved to 14-16 proteins |
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How are other Coronavirus genes transcribed?
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multiple 3-coterminally
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What kinds of diseases do Coronaviruses cause?
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common cold (30%)
SARS (severe exception) vet diseases |
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How are Coronaviruses spread?
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direct contact
aerosol fecal-oral contact with contaminated surfaces |
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Where did SARS come from?
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probably animal source; changed so it could infect humans via direct contact
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What is the fatality rate of SARS?
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10%
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What groups of Coronaviruses exist?
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I
II IIb (SARS III |
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Which protein binds to receptor?
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S
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How does the polymerase produce different mRNAs from one genome?
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polymerase recognizes 70bp leader region, then jumps to get different lengths of 3' elements
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Which mutation in SARS was associated with the jump to humans?
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29bp deletion alters ORF encoding an NS protein (unknown function)
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What is unique to Coronaviruses?
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a cell infected with 2 types has a high frequency of recombination by copy-choice mechanism (used as a lab tool)
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