Non-env RNA (Polio) Flashcards
Picornaviruses
Hepatitis A Enteroviruses - fecal-oral -> viremia - polio - coxsackie - ECHO - rhinovirus
Rhinovirus
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
Enteroviruses
Fecal-oral transmission Viremia -> different tissue tropism -> wide variety of disease All picornaviruses (+ RNA, unenveloped)
Coxsackie ECHO polio aseptic meningitis Hep A etc
Polio epidemiology
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%)
Types of antibody immunity
Active - make antibodies after infection/vaccine
Passive - given antibodies by MD, placenta
Passive->active - infected while passively immune -> mild disease -> active immunity
Clinical polio presentation
- subclinical
- mild/nonspecific ie fever
- aseptic meningitis (non-paralytic, H/A, fever, stiff neck)
- paralytic
- spinal (motor neurons -> withered leg)
- bulbar (resp center)
Polio pathogenesis
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)
Polio translational control
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
Polio polymerase
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
Polio capsid
Three proteins (VP1, VP2, VP3) -> beta barrel jelly roll (hollow icosahedral)
Receptor binding sites (CD155) in canyons
Generic replication strategies
Determined by - genome (RNA vs DNA) - absence of envelope (ex enterovirus no envelope bc low pH would remove) - permissivity of cell - receptors, innate defenses
Polio replication
+ 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)
Salk vaccine
Killed
Formaldehyde-inactivation -> not quite inactivated…-> deaths
- balance of killing virus without removing antigenicity
Requires boosters
Stable
Injection -> IgG
Sabin vaccine
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
Serology of polio
Three different serotypes
- no cross-neutralization
Vaccines must provide protection against all three
(each serotype also has three different capsomer proteins)
Live-attenuated vaccines
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
Polio eradication
Theoretically possible bc no animal reservoir
Socio-political issues
Need vaccine with low mutation/reversions
Post-polio syndrome
?? unknown mechanism
Mild polio -> muscle denervation -> slowly developing weakness
Can occur after vaccination
ECHO viruses
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
Random enteroviruses
EV 70 = acute hemorrhagic conjunctivitis
EV 71 = hand foot mouth disease, CNS
EV 72 = hepatitis A
Coxsackie viruses
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
Pleconaril
Trial chemotherapy
Bound to nucleocapsids of picornaviruses
-> Severe meningoencephalitis?
Reovirus
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
Adenovirus
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)
Gastroenteritis
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
Aseptic meningitis
Different causative agents
Seasonal
Enterovirus is most common cause
