Picornavirus Flashcards
enterovirus
poliovirus
coxsackievirus
echovirus
enterovirus
transmitted internalliny
picornovirus
small RNA virus
Hepatovirus
picornavirus
hep A (b and c are diff)
Rhinovirus
picornavirus
poliovirus structure
icosahedral symmetry
refers to geometric arrangement of subunits
best way to build a particle with a limited number of genes - few subunits
4 capsid
VP
viral proteins 1,2,3,4
4 on inside
make up capsud
high and low points are for cell surface binding sites
poliovirus genome structure
ss RNA +
5’ end - covalently linked to VPg protein, the UTR, the one ORF with polyproteins
single protein cut into 12 individual subunits by viral proteases
structural: VP1-4
non-structural: VpG, RNA dep. RNA pol
basic polio lifecycle
- receptor binding
- genome delivery into cytoplasm
- mRNA translation on ribosomes in cytoplasm
- polyprotein sythesis and processing (cut up all proteins)
- also, from + strand, negative strand synthesis inside membrane vesicle - make more negative and from that make a lot more positive
- virion assembly and release
8h
Picornavirus receptors
functions in uninfected cells = primary function is not to support virus entry! viruses have selected targets with mnormal cellular function
Ig-like receptors
integrins
etc.
RNA replication in poliovirus
22 aa VpG - covalent linkage to uridine, primes RNA synthesis!
- mRNA translation first, mRNA is in a loop, ribosomes make poly proteins
- ribosomes clear
- initiation of negative strand synthesis - pos makes a neg strand
- negative strand synthesis - 3D = RNA dep RNA polymerase, VpG is primer - makes complement strand
where does poliovirus replication occur?
on internal cell mebranes - vesicle formation in infected cells!
localizes and concentrates replication machinery
autophagy
leads to the destruction of cellular cytoplasmic constituents - double membrane sequesters part of cytoplasm and delivers contents to lysosome
PV causes cell stress that results in autophagy –> PV capitalizes on this response and blocks autophagy but uses vesicles for own development
how does poliovirus cause disease?
oral-fecal route via ingestion
virus enters via mucosal surface, enters blood through lymph, viremia in the blood spreads to neuromuscular junction by the muscles and then to CNS through axonal transport
can also cross blood brain barrier direcly
Poliovirus axonal spread
PV binds its receptor in neuromuscular junction, enters nerve, transported to spinal cord
where does poliovirus replicate?
in intestinal epithelium (including M cells)
in peyer’s patches
CD155
PVR
virus is released into neuromuscular junction
enters neurons through a CD155 interaction
taken up into vesicles and cytoplasmic tail is sticking out of vesicle surface
axonal transport with dyenin on microtubules
replicates in spinal cord
how does paralysis happen?
poliovirus replicates in neurons and destroys them, leading to paralyzation
IPV
inactivated poliovirus vaccine
must be injected
does not cause disease (when properly made)
does not produce intestinal immunity
used 1955-1961, 2000-present in US
OPV
oral poliovirus vaccine
easy to administer - no injection, drops, no dr
fraction of cost of IPV
produces intestinal immunity to interrupt WT virus transmission
better population immunity because passive transfer to non-immunized
usually reverts durng intestinal replication
eradicated polio in US and most of world still uses
How OPV is attenuated
eperical process, uses all 3 serotypes
passage in different hosts (animals/cells)
results in key genetic changes - mutations introduced by polio RNA pol
very few genetic changes needed to inactivate - most important is in 5’ UTR
Reversion of Sabin
virus reverts which is usually harmless to the recipient because their innate handles it while adaptive fights it off
vaccine strain replicates slowly and is ultimately cleared
but - it can spread in population and shed into the environment
natural selection in the environment! there is pressure to gain that mutation to make it WT
VDPV
vaccine derived poliovirus
VDPV regain virulence and spread in human populations
if immunocompromised - can have long ter persistence and excretion of WT polio
recent outbreaks - virulent revertants can ciruclate for years! very stable in the environment
picornavirus and pH
enterovirus - stable at low pH! fecal-oral need to be in GI
rhinovirus - respiratory, not GI - not stable at low pH
Echovirus
enterovirus
very similar to PV
associated w aspetic memningitis, rash, respiratory, myocarditis
no vaccine
Coxsackievirus
enterovirus
spread same as polio to viremia then differ in target
neonatal systemic illness
neuro illness
hand foot and mouth disease (rash)
implicated in diambetes
no vaccine
myocarditis - throught to be immune mediated! heart transplant
Coxsackie and myocarditis
immune response is destructive!
should be protective
Perforin - in CTL, if mice don’t have much less descruction of heart
Perforin does not effect growth of mice
Rhinovirus
typical picornavirus
NOT low pH resistant (like enterovirus)
cause of half of all common colds
Rhinovirus cell receptor
ICAM-1 or LDLR
how does rhinovirus cause illness?
infection: hand-nose, hand-eye
virus replicates in respiratory epithelium but does NOT cause cell damage
infection leads to production of inflammatory/immune mediators
cytokines - responsible for asthma and cold symptoms
