Simple +ssRNA viruses: Picornaviridae and Flaviviridae Flashcards
What type of genome do simple +ssRNA viruses have?
monopartite
What are two examples of simple +ssRNA viruses
Picornaviridae
Flaviviridae
What viral family does poliovirus belong to
Picornaviridae
What viral family does Rhinoviruses belong to
Picornaviridae
What viral family does Enteroviruses belong to
Picornaviridae
What viral family does Hepatitis A virus belong to
Picornaviridae
What are medically important human viruses that are in the Picornaviridae family
Poliovirus
Rhinovirus
Enteroviruses
Hepatitis A virus
What are morphological features of Picornaviridae viruses
pico means small so they are small RNA viruses
7500bp genome
non-enveloped
icosahedral capsid
During gene expression do Picornaviruses have a 3’ poly A tail or a 5’ cap or both
Picornaviruses have a 3’ poly A tail
they do not have a 5’ cap, a viral protein VPg is attached to the 5’ end instead
Without a 5’ cap how do picornavirus viral proteins get translated
use an internal ribosomal entry site IRES
they have a viral protein VPg attached to the 5’ end as well
What is the IRES and how is it used in Picornaviruses
Internal Ribosome Entry Site
It is located in this order 5’ of start codon, IRES, 3’ Vp6 (end of genome)
adopts a specific 3D conformation that allows it to bind to ribosomes and direct translation
What is inhibited during picornavirus gene expression, what does this lead to
cap-dependent translation is inhibited of the host translation
target eIF4GI and 46II for degradation, these are necessary host translation factors
the degradation of the above host factors leads to only the translation of viral proteins so only viral proteins are made
How are the genes of picornaviruses expressed
- genome is translated as one polyprotein
- the polyprotein is then cleaved at specific sites by viral proteases, protease specific for picornaviruses is 3C
- the rate of cleavage is distinct at each site dictating how much of each protein is made
- structural proteins are made at the 5’ end and non-structural proteins are made at the 3’ end
- release non-structural proteins first and release structural proteins after
What end are structural proteins made in the picornaviruses
5’ end form structural proteins and these are released after the non-structural proteins
What end are non-structural proteins made in the picornaviruses
3’ end form the non-structural proteins and these are released first before the structural proteins are
What cleaves a polyprotein
proteases
Where does picornavirus replication occur
occurs on double membrane vesicles that are derived from the ER or autophagic membranes
Where are the double membrane vesicles where picornavirus replication occurs derived from
from the ER or autophagic membranes
What has to happen in picornaviruses before replication can begin
replication first requires translation of viral proteins
Are polymerase and other replicase proteins present in the virion of picornaviruses
no
What happens after translation of viral proteins in picornaviruses
the virus must make - RNA
dsRNA intermediate
Where does initiation occur in picornaviruses
initiation must occur at the 3’ end of the genome
How is the genome held in picornavirus replication
genome is held in a circular form
What is the process of picornavirus genome replication
- genome is held in a circular form
- Host Poly A and Poly C binding proteins are brought together by 3CD protein
- 3CD is the precursor for the polymerase, 3D is the polymerase
- once it is ready to leave it is activated by proteolytic cleavage and replicates RNA from the 3’ end of the template
What is the role of Host Poly A and Poly C, viral 3DC and 3D in picornaviruses
picornavirus replication
genome is held in a circular form
Host Poly A and Poly C are binding proteins that are brought together by 3CD protein
3CD is the precursor of the polymerase
3D is the polymerase
once its ready to go, it is activated by the proteolytic cleavage and replicates RNA from the 3’ end of the template
In picornavirus replication, once RNA synthesis initially begins what happens
Once RNA synthesis begins, the polymerase proceeds along the entire length of the template RNA
3’ end of the template will become available for further replication before the first complexes are finished
up to five complexes can be formed on a genome
this is called the replicative intermediate or RI
dsRNA is likely unwound by the viral helicase (maybe 2C protein)
What is the replicative intermediate RI in picornaviruses
when the 3’ end of the template will become available for further replication before the first complexes are finished
up to five complexes can be formed on a genome
What is dsRNA likely unwound by in picornaviruses
viral helicase maybe 2C
How many complexes can be formed on a picornavirus genome
up to 5
replicative intermediates?
In picornavirus after -RNA synthesis what occurs
+ RNA synthesis occurs in much the same way
How does +RNA synthesis occur in picornaviruses
much the same way of -RNA synthesis
production of these RNA is asymmetric
much more + RNA is made than -RNA
only +RNA is release from replication complexes will be packaged into virions
In picornaviruses is more +RNA or -RNA made
more +RNA is formed
What type of RNA packaged into virions of the picornavirus
only +RNA is released from replication complexes and packaged into virions
How does the picornavirus know which one to package
packaging signals is only on the +RNA strand and not on the -RNA strand, therefore only +RNA is packaged into virions
What are medically relevant Flaviviridae
arboviruses
West Nile Virus
Zika Virus
Dengue Virus
along with many others
What are morphological features of the Flaviviridae family
+ssRNA
enveloped
virion is spherical
50um in diameter
What are the similarities between Flaviviridae and Picornaviridae gene expression, two main points
gene expression is very similar
genome is translated into a single polyprotein and cleaved by viral proteases
structural proteins at 5’ and nonstructural proteins at 3’ end
What are the differences between Flaviviridae and Picornaviridae gene expression
Flaviviridae have
have a 5’ cap
do not have a poly A tail
sfRNA: subgenomic flavirus RNA
What are sfRNA and what viral family are they located in
subgenomic flavirus RNA
found in Flaviviridae
Is sfRNA transcribed
it is not transcribed
How is sfRNA formed
it is NOT transcribed
it is the incomplete digestion of gRNA by cellular exoribonucleases
What is the function of sfRNA
has important functions countering IFN, RNAi, RNA decay and transmission
Where does Flavivirus replication occur
viral replication occurs on the ER-derived membranes that form viral factories
these are single membranes
What are the four viral proteins that are NOT transmembrane proteins in Flaviviridae
polymerase NS5
protease NS3
capsid protein
NS1
What is the role of NS5, NS3, capsid protein and NS1 in Flaviviridae and where are they located
not transmembrane
NS5: polymerase, needs to move so it cannot be embedded in the membrane
NS3: protease, has to cleave so it cannot be embedded in the membrane
capsid protein: capsid cannot be embedded in the membrane
NS1
Does it matter which side of the membrane the polymerase is on in Flaviviridae replication
yes, the membrane is not a straight line, its in some type of vesicle form, the RNA has to be exposed for translation at some point so the non-transmembrane protein have to be on the outside of the membrane and not transmembrane to help in this process
The genome of Flaviviridae and Picornaviridae both encode for what?
a polyprotein that is cleaved by viral proteases
When are replicative intermediates formed
during replication where multiple initiations occur, up to 5 complexes can be formed in the Picornaviridae
What does it mean by RNA replication is asymmetric
means that much more +RNA is produced that -RNA
Does the IRES allow for transcription, replication, or translation
translation
How do Picornaviruses prevent host translation
cap-dependent translation is inhibited —- host translation has 5’ cap
the virus targets the eIF4G and 46II for degradation (these are necessary host translational factors)
host translation is prevented so only viral proteins are made
How is the picornavirus polymerase activated
activated by proteolytic cleavage and replicates RNA from the 3’ end of the template
What does it mean if RNA virus replication is asymmetric
if RNA virus replication is asymmetric then much more + or - sense RNA is made over the other
if there was equal amounts then they would form together making dsRNA that would be recognized by the host
in picornavirus replication more + RNA is made than - RNA
Why do PV replicate asymmetrically
if RNA virus replication is asymmetric then much more + or - sense RNA is made over the other
if there was equal amounts then they would form together making dsRNA that would be recognized by the host
in picornavirus replication more + RNA is made than - RNA
