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Virology > Non-env RNA (Polio) > Flashcards

Non-env RNA (Polio) Flashcards

1
Q

Picornaviruses

A 
Hepatitis A
Enteroviruses - fecal-oral -> viremia
 - polio
 - coxsackie
 - ECHO
 - rhinovirus
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2
Q

Rhinovirus

A

Most common cold, also asthma exacerbation
- also corona, RSV, parainfluenza
Many antigenic types (80+)

Labile at low pH (-> enteroviruses?)
Need low temp (33 C)
Aerosol, very infectious

Too many serotypes for vaccine, symptomatic tx

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3
Q

Enteroviruses

A 
Fecal-oral transmission
Viremia -> different tissue tropism -> wide variety of disease
All picornaviruses (+ RNA, unenveloped)
Coxsackie
ECHO
polio
aseptic meningitis
Hep A
etc
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4
Q

Polio epidemiology

A

Epidemics only 20th century, developed countries

Poor hygiene -> mothers immune -> passive immunity -> mild/subclinical infection -> active immunity

Good hygiene -> no immunity -> susceptible -> paralysis more likely if infected as adult
(still rare: 0.1-1%)

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5
Q

Types of antibody immunity

A

Active - make antibodies after infection/vaccine
Passive - given antibodies by MD, placenta

Passive->active - infected while passively immune -> mild disease -> active immunity

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6
Q

Clinical polio presentation

A
  • subclinical
  • mild/nonspecific ie fever
  • aseptic meningitis (non-paralytic, H/A, fever, stiff neck)
  • paralytic
    • spinal (motor neurons -> withered leg)
    • bulbar (resp center)
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7
Q

Polio pathogenesis

A

Invasion

  • > multiplication in GI lymph nodes (-> fecal)
  • > primary viremia
  • > replication in central focus (ie CNS)
  • > circulating Ab (too late to prevent paralysis)
  • > 99% asymptomatic or symptoms (incubation 2-3 wks)
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8
Q

Polio translational control

A

Destroys CAP-binding protein (shuts down host)

Polio mRNA has Internal Ribosome Entry Site (IRES) in 5’ untranslated region

  • > recruits translation factors
  • > ribosome without CAP-binding protein
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9
Q

Polio polymerase

A

RNA-dependent RNA polymerase (coded by + RNA strand)

No proofreading!
-> errors/mutations -> rapid evolution, adaptation, reversion of attenuated vaccine
(ex attenuate by mutating IRES -> revert to wildtype)
Challenge for antivirals

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10
Q

Polio capsid

A

Three proteins (VP1, VP2, VP3) -> beta barrel jelly roll (hollow icosahedral)

Receptor binding sites (CD155) in canyons

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11
Q

Generic replication strategies

A 
Determined by
- genome (RNA vs DNA)
- absence of envelope
 (ex enterovirus no envelope bc low pH would remove)
- permissivity of cell
  - receptors, innate defenses
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12
Q

Polio replication

A

+ strand (m)RNA -> translation ->
polyprotein -> proteases cleave (some in cell) ->

  • more proteases
  • structural coat proteins
  • RNA dependent RNA polymerase -> (-) strand -> synthesis of new + strand

Only RNA is necessary for pathogenesis (+ strand can make polymerase)

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13
Q

Salk vaccine

A

Killed
Formaldehyde-inactivation -> not quite inactivated…-> deaths
- balance of killing virus without removing antigenicity

Requires boosters
Stable
Injection -> IgG

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14
Q

Sabin vaccine

A 
Attenuated live (usu in IRES)
Oral -> IgA and IgG response
 -> shedding -> spread immunity
 (do NOT shed once infected bc IgA neutralizes)
Long-term (no boosters)

BUT can revert to virulent -> spread of virus
don’t give to pregnant or immunosuppressed

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15
Q

Serology of polio

A

Three different serotypes
- no cross-neutralization
Vaccines must provide protection against all three

(each serotype also has three different capsomer proteins)

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16
Q

Live-attenuated vaccines

A

Mutants - select for greater virulence in new host/tissue and reduced virulence for human
- ex different tissue tropism, temperature sensitivity
Testing
- virulence/safety
- antibody response to wildtype (requires some replication!)
Preferable to killed
- lasts longer
- viral antigens -> infected cells -> MHC I -> CD8 immunity
Adverse effects = reversion
- no pregnant women (unknown fetal testing)
- no immunosuppressed

17
Q

Polio eradication

A

Theoretically possible bc no animal reservoir
Socio-political issues
Need vaccine with low mutation/reversions

18
Q

Post-polio syndrome

A

?? unknown mechanism
Mild polio -> muscle denervation -> slowly developing weakness
Can occur after vaccination

19
Q

ECHO viruses

A

Enteric cytopathic human orphan viruses
Picorna - similar to polio (+ RNA, unenveloped)
Fecal-oral, stable - ie daycare

Many serotypes -> outcomes

  • > rash
  • > aseptic meningitis (leading cause)

No vaccine or tx

20
Q

Random enteroviruses

A

EV 70 = acute hemorrhagic conjunctivitis
EV 71 = hand foot mouth disease, CNS
EV 72 = hepatitis A

21
Q

Coxsackie viruses

A

Picorna - similar to polio (+RNA, unenveloped)
Fecal-oral, stable (ie daycare)

Group A -> skin and mucous
- herpangina (throat vesicles), hand/foot/mouth, meningitis
Group B -> viscerotropism
- myocarditis (neonates), meningitis, pleurodynia (intercostals), orchitis

No vaccine or therapy
Tx empirically
Can identify through isolation, antibody titers, PCR of CSF

22
Q

Pleconaril

A

Trial chemotherapy
Bound to nucleocapsids of picornaviruses

-> Severe meningoencephalitis?

23
Q

Reovirus

A

Respiratory enteric orphan virus

Icosahedral
10 segments of ds RNA + virion RNA polymerase -> mRNA
- genome not infectious
Non-enveloped

Fecal oral -> rotavirus -> infant diarrhea (most commont cause) -> mortality
Vaccine withdrawn dt intussusception
New vaccines = rotarix (live attenuated), rotateq (bovine)
Treat dehydration

24
Q

Adenovirus

A

Double-strand linear DNA (one segment)
Non-enveloped
Regulated mRNA and protein synthesis
- ex early machinery mRNA -> late/structural proteins
- virion synthesis in nucleus
Stable when dry -> airborne transmission -> 3-10 day incubation

Respiratory, tonsils
Epidemic kertoconjunctivitis
Gastroenteritis (enteric, fecal-oral)

25
Q

Gastroenteritis

A

All fecal oral
Mostly NOT enteroviruses

Rotavirus (reo) - 
 - multiple ds RNA
 - 0-18 months, highly infectious, 2 day incubation
Enteric adenovirus
 - single ds linear DNA
 - 0-24 months
Calcivirus (aka Norwalk)
 - (+) RNA, small, non-enveloped
 - Noro/Norwalk -> adolescents/adults, self-limiting, type O susceptible, vaccine in dev't
 - other strands -> infants
Astroviruses
 - (+) RNA
 - all ages
26
Q

Aseptic meningitis

A

Different causative agents
Seasonal

Enterovirus is most common cause

Virology (16 decks)

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