Picornavirus

Question 1

enterovirus

Answer 1

poliovirus

coxsackievirus

echovirus

enterovirus

transmitted internalliny

Question 2

picornovirus

Answer 2

small RNA virus

Question 3

Hepatovirus

Answer 3

picornavirus

hep A (b and c are diff)

Question 4

Rhinovirus

Answer 4

picornavirus

Question 5

poliovirus structure

Answer 5

icosahedral symmetry

refers to geometric arrangement of subunits

best way to build a particle with a limited number of genes - few subunits

4 capsid

Question 6

VP

Answer 6

viral proteins 1,2,3,4

4 on inside

make up capsud

high and low points are for cell surface binding sites

Question 7

poliovirus genome structure

Answer 7

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

Question 8

basic polio lifecycle

Answer 8

1. receptor binding
2. genome delivery into cytoplasm
3. mRNA translation on ribosomes in cytoplasm
4. polyprotein sythesis and processing (cut up all proteins)
5. also, from + strand, negative strand synthesis inside membrane vesicle - make more negative and from that make a lot more positive
6. virion assembly and release

8h

Question 9

Picornavirus receptors

Answer 9

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.

Question 10

RNA replication in poliovirus

Answer 10

22 aa VpG - covalent linkage to uridine, primes RNA synthesis!

1. mRNA translation first, mRNA is in a loop, ribosomes make poly proteins
2. ribosomes clear
3. initiation of negative strand synthesis - pos makes a neg strand
4. negative strand synthesis - 3D = RNA dep RNA polymerase, VpG is primer - makes complement strand

Question 11

where does poliovirus replication occur?

Answer 11

on internal cell mebranes - vesicle formation in infected cells!

localizes and concentrates replication machinery

Question 12

autophagy

Answer 12

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

Question 13

how does poliovirus cause disease?

Answer 13

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

Question 14

Poliovirus axonal spread

Answer 14

PV binds its receptor in neuromuscular junction, enters nerve, transported to spinal cord

Question 15

where does poliovirus replicate?

Answer 15

in intestinal epithelium (including M cells)

in peyer’s patches

Question 16

CD155

Answer 16

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

Question 17

how does paralysis happen?

Answer 17

poliovirus replicates in neurons and destroys them, leading to paralyzation

Question 18

IPV

Answer 18

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

Question 19

OPV

Answer 19

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

Question 20

How OPV is attenuated

Answer 20

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

Question 21

Reversion of Sabin

Answer 21

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

Question 22

VDPV

Answer 22

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

Question 23

picornavirus and pH

Answer 23

enterovirus - stable at low pH! fecal-oral need to be in GI

rhinovirus - respiratory, not GI - not stable at low pH

Question 24

Echovirus

Answer 24

enterovirus

very similar to PV

associated w aspetic memningitis, rash, respiratory, myocarditis

no vaccine

Question 25

Coxsackievirus

Answer 25

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

Question 26

Coxsackie and myocarditis

Answer 26

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

Question 27

Rhinovirus

Answer 27

typical picornavirus

NOT low pH resistant (like enterovirus)

cause of half of all common colds

Question 28

Rhinovirus cell receptor

Answer 28

ICAM-1 or LDLR

Question 29

how does rhinovirus cause illness?

Answer 29

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