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89 Cards in this Set

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How many genera of picornavirus are there?
5
What are the genera of picornavirus based on?
physical properties
serological relatedness
nucleotide sequence
Which genera does poliovirus belong to?
enterovirus
T/F: poliovirus is acid sensitive
F. can survive <pH 3
limited replication of poliovirus occurs in ___. extensive replication occurs in ___, the natural habitat
oropharynx
lower intestinal tract
What are enteroviruses sensitive to?
chlorine (0.3 to 0.5 ppm)
formaldehyde
T/F: presence of organic matter may protect poliovirus
T
What is the disease paralytic poliomyelitis charcterized by?
flaccid muscular paralysis (death of motor neurons)
Onnly __% of poliovirus infections result in clinical disease
1
Describe the poliovirus genome layout
one ss(+)RNA
5'-VPg-Long UTR-P1-P2-P3-Short UTR-polyA Tail-3'
T/F: the genomic poliovirus RNA is infectious by itself
T
Which end of the poliovirus genome has the shorter UTR
3' end
What is the poliovirus 3' UTR important for?
synthesis of (-) strand for replication of genome
What is the poliovirus 5' UTR important for?
translation of the RNA and possibly packaging of genome into capsids
How many proteins does the genome encode? How long is/are this/these protein(s)?
one polyprotein (2100-2400 amino acids), cleaved to make 20 proteins
What is VPg? How long is it?
A small basic protein 23 amino acids long
Describe the poliovirus morphology
non-enveloped
27-30 nm
icosahedral capsid with 20 capsomer
How long is the genome stretched out?
2500 nm
How is the large genome packaged in such a small space?
Na and K ions inside the capsid counteract the negative charges of the phosphate groups of the RNA
Describe the poliovirus capsids
icosahedral
20 capsomer
each capsomer=three small triangular subunits (T=3)
each subunit has one copy of each of VP0,VP1,VP3
How many protein molecules in total make up the poliovirus capsid?
180 protein molecules
poliovirus VP0 is cleaved to make __ and __ during maturation
VP2, VP4
VP_ is localized to outside
VP_ is localized to inside
VP2
VP4
What is poliovirus host range?
humans only
Can transformed monkey cells be infected with poliovirus? Mouse cells?
yes
no
What are the receptors for poliovirus?
normal cellular proteins called CD155
CD155 is a member of the __ gene superfamily
Ig superfamily
(Ig and other cell surface molecules such as CD4, CD8, MHC Class I and II)
What does the Ig gene superfamily include?
Ig and other cell surface molecules such as CD4, CD8, MHC Class I and II
Where is CD155 expressed?
monocytes, macrophages, thymocytes, and CNS neurons
Monocytes are a type of ___ that can mature into ___ in various different tissues
leukocyte
macrophages
Thymocytes are ___ precursors which develop in the ___
T-Cell
Thymus
What is the first step poliovirus replication cycle?
attachment to CD155
Does poliovirus leave its capsid at the front door, or does it uncoat inside an endosome?
this is currently unknown
What results from the binding of poliovirus to the cell surface?
a conformational change leading to loss of VP4 protein
RNA genome then released into cytoplasm thru membrane channel formed by VP1 proteins
The RNA genome of poliovirus is released into the cytoplasm of the host cell through a ___ formed by ___ proteins
membrane channel
VP1
T/F: During entry a conformational change results in loss of VP2 protein from the virus particle
F. VP4 is lost.
How does poliovirus compete with the cellular mRNA for the ribosomes?
the cap-binding complex binds to the 5' methylated cap of the cellular mRNAs, preventing binding to ribosomes

this shuts off cellular protein synthesis
How quickly can poliovirus shut off cellular protein synthesis after arrival?
within 30 minutes
T/F: the poliovirus has a 5' capto facilitate binding to the ribosomes
F. It lacks a 5' cap and must rely on the IRES
What is IRES?
Internal Ribosome Entry Site
A secondary structure formed by RNA folding, due to H-bonds between complementary bases
What is the function of IRES?
It facilitates binding of the RNA to the ribosomes
The ___ sense RNA is ultimately packaged inside the new poliovirus capsid
(+)
Translation of the poliovirus RNA is initiated at the IRES internal site ___ nucleotides from the ___ end, resulting in production of the polyprotein
741
5'
What carries out several sequential cleavages of the polyprotein during and after its synthesis? What does the first set of cleavages yield?
The polyprotein cleaves itself. As it acquires secondary and tertiary structure, part of it becomes an active protease

P1, P2, P3
P1 contains ___
P2 contains ___
P3 contains ___ proteins
structural proteins
proteases
proteins involed in RNA synthesis (Vpg and RDRP)
What three components comprise the poliovirus "replication complexes"?
RDRP
Vpg
genomic (+) strand of RNA
What dorms the "replication compartment" during poliovirus replication cycle?
the replication complexes (RDRP, Vpg, (+) genomic RNA) and cellular membrane structures
Where does poliovirus RNA synthesis occur?
in "replication compartments" derived from virus-modification of the endoplasmic reticulum
What are "replication compartments"?
compartments derived from virus-modified ER
The __ strand in the replication compartment serves as the template for synthesis of new (+) strands of RNA, some of which are translated by cellular ribosomes
(-)
What is poliovirus P1 cleaved to produce?
all the coat proteins = VP0, VP1, VP3
VP0 VP1 and VP3 associated to form the ___. The viral genome is then inserted into it.
pro-capsid
What is the PAC site?
a short nucleotide sequence in the (+) strand of RNA that interacts with the capsid proteins ensuring that the (+) strand (not the (-) one) is packaged into the capsid
What ensures that (+) and not (-) strand RNA gets packaged?
the packaging (PAC) site in the (+) strand
VP0 is cleaved after...
the genome is inserted into the pro-capsid
What process is referred to as 'maturation' of the poliovirus?
cleavage of VP0 -> VP2 and VP4

happens after genome insertion into pro-capsid
How does the RNA genome catalyze the cleavage of VP0 during maturation?
It acts as a ribozyme (an RNA molecule with enzymatic activity)
Define ribozyme
an RNA molecule with enzymatic activity
When is poliovirus released from the cytoplasm?
When the host cell lyses
Is poliovirus RDRP more similar to our cellular DNA polymerase or RNA polymerase?
DNA polymerase, because RDRP requires a primer when synthesizing
What is the function of poliovirus RDRP?
to copy RNA
What is the sequence of nucleotides in Vpg?
5'-pUpU-OH-3'

p=phosphate
U=uracil
What critical group does a primer provide during initiation of RNA synthesis?
3-OH group
In RNA synthesis, nucleotides are attached to the ___ end of Vpg
3'OH
Define primer
a molecule to which the polymerase can attach the first nucleotide during replication
To copy (+) RNA, a replicative intermediate (-) strand is created. How many Vpg molecules are used in total to get from (+) to (+)?
2
t/f: THE poliovirus RNA polyA tail binds to the Vpg during genome replication
t
What is the portal of entry for poliovirus?
alimentary trans via the mouth
What is the poliovirus incubation period?
7-14 days
What is the primary site of infection of poliovirus ?
lymphoid tissue associated with the oropharynx (throat) and gut
Virus production at the primary site of infection (throat or gut lymphoid tissue) may lead to...
transient viremia which delivers virus to target organs of the CNS
How long does poliovirus usually stay in the oropharynx after infection?
1-2 weeks
How long is poliovirus shed in the feces?
several weeks
What are the four outcomes of poliovirus?
subclinical
mild (abortive) polio
non-paralytic poliomyelitis (aseptic meningitis)
paralytic poliomyelitis
What is the most common form of the polio disease?
abortive

recovery in a few days, non-specific symptoms (fever, malaise, headache, nausea, vomiting)
Describe non-paralytic polio
ALso known as aseptic meningitis

stiffness/pain in neck and back 2-10 days

rapid recovery
Describe paralytic polio
motor neuron damage

recovery within 6 months
Do antibodies appear early or late in poliovirus infections?
early
What is post poliomyelitis muscle atrophy
a reapparance of paralysis decades after illness due to normal decline in function of motor neurons that had compensated for the loss in function of the killed motor neurons during polio infection
How many poliovirus serotypes are there?
three - 1,2,3
T/F: the different serotypes of poliovirus may elicit the production of some of the same antibodies
F. Distinct populations of antibodies will be made
T/F: Infection by one serotype of poliovirus confers protection againts other serotpyes
F
Where are the epitopes responsible for Ab production located? Mostly located?
VP1,2,3
mostly VP1
What are the two forms of poliovirus vaccination? Describe them.
IPV - inactivated, injected, cultivated in monkey kidney cells and deactivated with formaldehyde
OPV - oral live attenuated cultivated from monkey kidney cell culture
What does IPV NOT do? What is the implication?
confer localized immunity thru IgA Ab secretion into mucosal lining of GI tract

infected people would be protected, but would still shed poliovirus in thier feces and could transmit it
What is the problem with OPV?
low rate of mutation - can revert back to virulent form

shed in the feces of the vaccinated recipient for weeks and can be disseminated to others
Why would initially administering IPV, then doing OPV booster be good?
IPV -> serum antibodies
Then, if OPV reverts to virulent form person will be protected
Does IPV confer humoral immunity?
yes
Which is more expensive, IPV or OPV?
IPV