ICL 1.3: RNA Viruses - Poliovirus Flashcards
which property is unique to viruses?
A. they are small in size B. they replicate only intracellularly C. their genome can be made of RNA D. infection involves receptor binding and endocytosis E. outer lipid membrane
C. their genome can be made of RNA
what is the name of the viral structure composed of the genome enclosed in a protein coat?
nucleocapsid
what are the characteristics of the Picornaviridae family?
single stranded RNA virus
positive sense
naked
which polymerases does viral RNA replication use?
RNA dependent RNA polymerase
RNA dependent DNA polymerase
if the first function is nucleic acid synthesis, polymerases must be virion-associated
**virion-associated polymerases are packed into the particle itself to be used immediately after entry
what determines the replication strategy of a virus?
it’s genome!
what are the two classes of RNA viruses?
- strand RNA viruses
2. - strand RNA viruses
what are + strand RNA viruses?
their genome is mRNA that can be directly translated into protein by host ribosomes!***
so the first thing that happens when the viral RNA enters the cell is translation into proteins
this means that the RNA genome by itself is infectious!! it will initiate a complete replication cycle all on its own because it can be directly made into proteins by host ribosomes
what are - strand RNA viruses?
their genome is a complement of viral mRNA so it can NOT be directly translated into protein – instead they serve as templates for mRNA synthesis after entry
first, mRNA has to be synthesized by virion-associated polymerases because host polymerases only read DNA and don’t recognize RNA
so the naked genome of -strand RNA viruses is NOT infectious
which families of RNA viruses are naked virions?
- Picornaviruses
- Caliciviridae
- Hepeviridae
they’re all icosahedral symmetry
which families of RNA viruses are enveloped virions?
- Togaviruses
- Flaviviruses
- Coronaviruses
they’re all pleomorphic symmetry
which virus family is poliovirus part of?
picornaviruses
aka a naked, positive strand RNA virus with icosahedral symmetry
there are 3 polio subtypes: 1,2,3
does poliovirus have virion-associated polymerase?
nope
since it’s + strand, there is no virion-associated polymerase and the RNA genome is translated directly by host ribosome
what happens during the attachment phase of replication for polio?
the polio capsid canyon region specifically binds to host cell at CD155 = PVR
PVR = poliovirus receptor
this happens at 0 - 4°C in the lab so it’s a super strong binding, no energy is needed
which cells does polio infect?
only cells with CD155!
this means that there is a very narrow range for polioviruses as only humans and some primates are hosts and only some human cell types express CD155
so this means that the presence of the host receptor, called PVR for poliovirus receptor, on the surface of cells is a major determinant of host range!!
which proteins are in the capsid of poliovirus?
VP1-4
what is the structure of PVR?
PVR - poliovirus receptor
it’s an immunoglobulin
what is the canyon of a poliovirus?
it’s the specific part of the poliovirus capsid that binds to the host PVR (CD155)
what does the WIN compound do?
it’s an inhibitor that blocks the poliovirus from binding to host cells
it does this by binding to the canyon region of the capsid
however, viruses mutate to evade this inhibition
what happens during the uncoating phase of replication for polio?
a conformational change happens to the virion from binding the PVR leads to genome entry into the cytoplasm
the naked RNA binds ribosomes for translation
the RNA genome has a VPg protein that covalently attaches at the 5-end but it’s NOT a cap
what is the function of the VPg?
VPg = virion genome protein
it’s a protein that’s part of the poliovirus RNA genome
it’s a virus-encoded protein that’s covalently attached to the 5’ end of poliovirus virion RNA
VPg is a structural protein that acts as a primer for both - and + strand RNA synthesis!
what happens during the synthesis phase of replication for polio?
nucleic acids and proteins are synthesized!
- one long polyprotein is synthesized from host ribosomes
- the polyprotein is cleaved into P1, P2 and P3
- P1 is cleaved into VP0, VP1 and VP3
VP0 is cleaved into VP4 and VP2
VP1-4 make up the capsid of the virion!
- P2 turns into 21 protease
- P3 is cleaved into VPg and a polymerase
where does poliovirus RNA synthesis occur?
the cytoplasm!!!
how does RNA synthesis occur for the poliovirus?
- (+) genome RNA is copied into complementary (-) RNA templates with VPg-covalently coupled to the 5’end of each RNA
VPg acts as the primer for initiation of each RNA strand, both - and +!!
- then the (-) RNA is copied many times to produce a large excess of (+) RNA
each (+) RNA strand will have a VPg coupled to its 5’ end
while RNA replication is happening, there exists a replicative intermediate (RI) which is partially dsRNA that is made of the the template (-) RNA strand, polymerase and nascent (+) product strands
what is RI?
RI = replicative intermediate
part of the poliovirus synthesis phase of replication
it is partially dsRNA that is made of the the template (-) RNA strand, polymerase and nascent (+) product strands
