Picornavirus & Polio Flashcards
(28 cards)
Structure of picornavirus
- small, non-enveloped, icosahedral virus
- ss (+) sense RNA
Which picornaviruses are acid stable?
- Enterovirus
2. Hep A virus
Clinically important picornaviruses:
o Poliovirus o Coxsackieviruses (serotypes A and B) o Echoviruses o Enteroviruses o Rhinoviruses And Hep A (non-enterovirus)
What is true of genetic information transfer within species groups?
Recombine in the wild to become more virulent.
Can also recombine across species groups (cross-species sex does not lead to more fit viruses = they don’t transmit)
What molecules of the virus and host define serotypes?
- Neturalizing antibodies from the host
- Antigenic epitopes of capsid proteins (on the surface of virus particles)
What is recognized by antibodies to neutralize infectivity?
The epitopes on capsid proteins (particular flavors for each virus)
Immunity to one serotype IS/IS NOT protective against other serotypes?
IS NOT protective - this is why it is the most infectious virus…
Most common outcome of picornavirus infection?
- Asymptomatic infection (coexist well together, and try not to kill host)
Diseases caused by picornavirus
- Aseptic meningitis
- Encephalitis
- Paralysis (AFP)
- Respiratory illness
- Myocarditis
- Hand-Foot-Mouth Disease
Cause of myocarditis in newborns, adolescents or young adults? Who has the most severe disease?
Coxsackie B virus
Neonates have more severe disease
What molecules of the virus and host define picornavirus serotypes?
Serotypes of picornoviruses are related to both viral and host elements. Serology is determined by antigenic epitopes of viral capsid proteins to which the host makes neutralizing antibodies. Serotypes require both the antigen and antibody.
What months do you usually get enterovirus?
Late summer and early fall (June - Oct)
Common presentations of enterovirus
- Children: Fever, rash & exanthem
- Adults: Aseptic meningitis b/c adults tolerate this poorly
- Both: URIs
Why are the organisms causing meningitis in newborns different from those in children > 6 months of age?
Maternal antibodies - newborns have them… because mom has been exposed before she had the baby.
What is the “protective immune response” to the organisms causing meningitis in children > 6 months of age?
Antibodies! All 3 are encapsulated, so antibodies to the capsules. You must have a B-cell response.
Picornavirus particles
- icosahedron
- 60 copies of each capsid protein (+vRNA)
- No replication proteins in virus particles
(stable and resistant in the environment b/c naked virus particle)
Replication of (+) strand RNA viruses
- Exclusively in the cytoplasm
- Virions DO NOT contain replication proteins
- Virion RNAs have 3 functions:
- genome: packaged in virion
- viral mRNA: translated into viral replication proteins
- template RNA: copied into (-) strant RNA for replication
- Viral RNA dependent RNA polymerase has an error rate (1 every 5000 to 10000 bases)
(+) RNA –> (-) RNA –> (+) RNA
Pathogenesis of picornavirus
- Primary infection @ mucosal surfaces
- Viremia tries to infect target organs
- Interferon stimulated genes limit the tissue tropism and amount of replication
- Neutralizing IgG antibodies in the blood block viremia, and disease but NOT infection so you don’t usually get the virus affecting the target tissue
- IgA antibodies are necessary at mucosal surfaces.
Poliovirus pathogenesis
Day 0: Ingest fecal material
Day 1-2: Low level viremia
Day 2-7: Amplified viremia
Day 7-14: CNS infection
Poliovirus infection outcomes
90-95% inapparent infection
4-8% Minor illness (URI)
1-2% Aseptic meningitis
0.1-2% Paralytic poliomyelitis
How does Polio get to the brain?
- Across the BBB
- Infect motor neurons in muscle and goes retrograde as they are replicating. This is UNILATERAL paralysis in the limb that was infected. Sensory neurons are unaffected.
IPV
Advantages:
- Killed Wildtype Poliovirus
- Injected
- No vaccine-Associated disease
- Protected Systemic Immunity (IgG)
Disadvantages:
- Limited mucosal immunity - can still be infected, just may not develop illness
- Expensive compared to OPV
- Injected
OPV
Advantages:
- Live attenuated
- Oral admin
- Inexpensive
- Systemic and mucosal immunity (IgA and IgG)
Disadvantages:
- Vaccine Associated Paralytic Poliomyelitis (VAPP)
- Shed revertant poliovirus
- Contraindicated in immunocompromised, ESPECIALLY B-CELL deficiency
VAPP and OPV epidemiology
(1961-2003 data; recognized in 1960s when OPV was started)
- As soon as US stopped using OPV, VAPP went away
- 1 - 2 billion doses of OPV still used per year, with 250-500 cases of VAPP (but not in the US)