Viral Gastroenteritis Flashcards

1
Q

Viruses that can cause gastroenteritis

A
  • Norovirus (Calciviridae)
    • Single RNA (+) sense
  • Rotavirus (Reoviridae)
    • Double shell, 11 genome fragments of dsRNA each encode single protein
  • Astrovirus
    • Non-enveloped ss(+)RNA virus
  • Enteric adenovirus
    • Icosahedral DNA virus
  • Picobirnaviruses
    • Icosahedral DNA virus
  • Bocavirus
    • Icosahedral DNA virus
  • Coronavirus
    • (+) strand RNA genome
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2
Q

Norovirus: details and serotypes

A
  • Single RNA (+) sense
  • Foods, water, shellfish
  • 50% attack rate 2 days; need only 10 to get it
  • Genogroups: GI, GII, GIV
  • Most common cause of gastroenteritis
  • Serotypes:
    • Norwalk
    • Hawaii
    • Montgomery
    • County
    • Cockle agent
    • Snow Mountain agent
    • Marin County agent
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3
Q

Rotavirus: details and serotypes

A
  • Double shell, 11 genome fragments of dsRNA each encode single protein
  • Vaccine –> decreased incidence
  • 2 capsids:
    • Outer = VP7
    • Spike protein = VP4
  • NSP4 = enterotoxin; non-structural protein
  • 3rd most common cause of gastroenteritis
  • Require trypsin activation for virulence
  • Serotypes 1-4 of 9 total
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4
Q

Astrovirus: details and serotypes

A
  • Non-enveloped ss (+) RNA virus
  • 2nd most common cause of gastroenteritis
  • Can cause viremia - newer discovery
  • 7 serotypes identified
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5
Q

Diagnosis of gastroenteritis viruses

A
  • Most viruses can’t be isolated in cell cultures
  • History –> virus more likely to cause vomiting
    • Also has rapid onset, shorter duration compared to bacterial
  • Use data –> viral antigen detection arrays + PCR
    • Newer tools used for identification, only recently available
  • Norovirus: ELISAs and RIAs to detect norovirus antigens in stool
    • RT-PCR more sensitive, used to differentiate strains by RT-PCR of less conserved genes (e.g. capsid)
  • Rotavirus: ELISA or rotazyme test
    • RT-PCR can identify virus antigens or RNA in stools quickly
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6
Q

Rotaviruses: replication and pathogenesis

A
  • Double shelled with 11 genome segments of dsRNA
  • Contains dsRNA-dependent RNA polymerase and other enzymes
  • Each genome segment encodes ss-mRNA which makes one protein
  • Reassortment of genome segments occurs whenever two different rotaviruses infect the same cell
  • Rotavirus virions assemble at RER –> inner cores are enveloped in transient envelope –> loses lipid –> becomes outer protein shell of virion in lumen of RE
  • Virions NOT infectious unless activated by treatment with trypsin
    • Trypsin available naturally in gut
    • Trypsin cleaves outer capsid protein & aids in virus uncoating
  • NSP4 (viral non-structural protein) = secreted enterotoxin that increases intracellular Ca2+ levels in infected cells –> alters signal transduction –> alters ion transport in intestinal epithelial cells –> diarrhea
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7
Q

Norovirus: replication

A
  • Genomes are 7.7kb, ssRNA (+) messenger sense
  • Genome includes:
    • ORF1 at 5’ end
      • Encodes RNA-dependent RNA polymerase and structural proteins
    • ORF2
      • Encodes capsid and major viral capsid protein VP1
    • ORF3 at 3’ end
      • Encodes minor, highly variable structural protein VP2
  • Cleavage of viral polyproteins by virus-encoded protease required for virus replication
  • Virus-encoded protease is potential drug target
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8
Q

Most likely virus causing epidemic in nursery

A

Rotavirus

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9
Q

Most likely virus causing epidemic in daycare

A

Astrovirus - identified in 34% of daycare center outbreaks

Rotavirus

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10
Q

Most likely virus causing epidemic in school

A

Astrovirus, Norovirus

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11
Q

Most likely virus causing epidemic in nursing home

A

Astrovirus, Norovirus

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12
Q

Most likely virus causing epidemic in contaminated shellfish

A

Norovirus

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13
Q

Most likely virus causing epidemic in water

A

Norovirus

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14
Q

Type of immunity most likely to prevent viral gastroenteritis

A
  • Humoral immunity
  • Only lasts for a few months
  • Different serotypes prevent cross-immunity
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15
Q

Vaccines for norovirus

A
  • Would need several serotypes
  • Plants have norovirus protein & recombinant ones that are vaccine candidates
  • Insect cells can also assemble capsids
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16
Q

Vaccines for rotavirus

A
  • Rotateq
    • Pentavalent live attenuated bovine vaccine
  • Rotarix
    • Monovalent live attenuated human rotavirus
  • Synthetic peptides being explored
  • Insects can make particles but cost $$$
  • Plants like bananas and potatoes can make them too
17
Q

Role of virus-encoded enterotoxin in viral gastroenteritis

A
  • NSP4 - viral enterotoxin for rotavirus
    • Causes havoc on small intestine
    • Secreted enterotoxin that increases intracellular Ca2+ levels in infected cells & cells inoculated with NSP4
    • Alters signal transduction & ion transport in intestinal epithelial cells
    • Overall effect: secretion of chloride from epithelial cells in small intestine –> secretory diarrhea
    • Has to be in the gut in order to be effective
    • Could possibly be a drug target