Yoshimura: Viral Gastroenteritis Flashcards by Andrew Kumar

What is gastroenteritis?

What percentage of acute diarrhea is viral?

Gastroenteritis: inflammation of the lining of the intestine, leading to diarrhea

More than ½ of all cases of acute diarrhea are of viral origin

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Gastroenteritis

Incubation period:

What does dehydration result from?

Incubation period of 1-4 days before abrupt onset of vomiting, followed by diarrhea and mild fever

Dehydration results due to severe loss of electrolytes and fluids (can be fatal if untreated)

Note: Second only to acute respiratory infections as a cause of disease in families.

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What viruses are responsible for gastroenteritis (4)?

Reoviridae (Respiratory and enteric orphan virus)
Adenovirus (Types 40 and 41)
Calcivirus
Astrovirus

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Reoviridae (Respiratory and enteric orphan virus):

Type of genome?

What is the most important cause of severe gastroenteritis in young kids?
Segmented?
Groups?

Reoviridae (Respiratory and enteric orphan virus): dsRNA genomes (cytoplasmic replication)

Rotavirus: most important cause of severe gastroenteritis in young kids

Segmented, linear dsRNA genome
Groups A, B, C and D (Group A usually associated with human gastroenteritis)

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What is the second most important viral agent of endemic diarrhea in children?

Type of genome?

Adenovirus (Types 40 and 41): DNA genome (nuclear replication)
o Second most important agent of endemic diarrhea in children

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Calcivirus

Type of genome?

What is the most common cause of outbreaks of acute, nonbacterial gastroenteritis in the USA?
Who are affected?

Calcivirus: +ssRNA genome (cytoplasmic replication)

Norovirus (Norwalk Virus): Most common cause of outbreaks of acute, nonbacterial gastroenteritis in the USA

1 in 15 people in the US get norovirus illness each year
Older children and adults are affected.

(Natalja’s notes)
Norovirus (Norwalk Virus): 40% of outbreaks of acute, epidemic, nonbacterial gastroenteritis in the US; mainly affects older children and adults

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What virus causes sporadic cases and occasional outbreaks in infants, young children and the elderly?

Type of genome?

Severity?

Astrovirus: +ssRNA genome (cytoplasmic replication)
o Causes sporadic cases and occasional outbreaks in infants, young children and the elderly (those that do not have robust immune systems)
o Infections are usually mild

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Rotavirus

Transmission Route:

Site of Infection:
-Which sites are spared?

Infectious Dose:

Transmission: Fecal-oral route; nosocomial infections also frequent (ubiquitous organisms)

Site of Infection: Cells at the tip of villi in the small intestine (stomach and large intestine are spared)

Infectious Dose: As few as 10 ingested particles are all that is required; after infection, a very large number of particles appear in the feces (~10^10)

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What family is rotavirus a part of?

Reoviridae

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Rotavirus

Incubation Period:

Seasonality:

Common Age Groups:

Incubation Period: 1-4 days

Seasonality: Infections predominate during the winter season

Common Age Groups: Most common age affected is children between 6 months and 2 years.

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Rotavirus
Mechanism of Pathogenesis

Direct or indirect cellular damage?
What does the outer viral capsid protein bind to?

Direct Cellular Damage: viral outer capsid protein binds to a glycolipid receptor on enterocytes

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Rotavirus
Mechanism of Pathogenesis: Direct cellular damage

Where does replication occur?
What occurs after replication?
How are transport mechanisms affected?

Replication in cytoplasm; after replication, there is acute onset of vomiting and diarrhea

Damage to transport mechanisms (impaired Na and glucose absorption)

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Rotavirus
Mechanism of Pathogenesis
Activation of Intestinal Nerves

What is stimulated?

Activation of Intestinal Nerves: stimulation of enterocytes to secrete water

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Rotavirus

Mechanism of Pathogenesis (3):

Direct cellular damage

Activation of intestinal nerves

Fluid accumulation in the lumen of SI

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Rotavirus
Mechanism of Pathogenesis

What does fluid accumulation in the lumen of the small intestine result in?

10-20 diarrheal episodes per day and severe dehydration

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Rotavirus
Structure

Enveloped?
Shape:
Stable?

Basics: unenveloped, icosahedral virus with triple-shelled protein capsid

Very Stable: resistant to extreme ionic strengths, ranges of pH and temperatures up to 55 degrees C; virions are stable in aerosols (especially at high humidity)

Rotavirus
Genome

Linear?
Segmented or non-segmented?
Genome type:

Linear, segmented (11 segments), dsRNA

Rotavirus
Genome

What does each segment encode?
What about reassortment?
Recombination?

Each segment encodes at least 1 protein

Segments from different viruses can reassort with high frequency, leading to rotavirus evolution

No evidence for recombination between RNA molecules

Rotavirus
Life Cycle

Attachment: What binds to what?
Entry mediated by?
Where does uncoating of the outer shell occur?

Attachment: viral capsid (VP4) binds to cellular receptors (sialic acid and integrins)

Entry: receptor mediated endocytosis

Uncoating of Outer Shell: occurs in lysosome

Rotavirus
Life Cycle

What is transcribed to mRNA?
What is each step in transcription and capping mediated by?

–RNA strands transcribed to +mRNAs: each step in transcription and capping is mediated by an enzyme present in the virion and encoded by a viral gene

Rotavirus
Life Cycle

What is replicase?
What is used for translation in viral proteins?

Replicase (RNA-dependent RNA Polymerase)

+mRNAs used for translation of viral proteins

Rotavirus
Life Cycle

When does assembly of new –RNA occur?
What synthesizes –RNA from +mRNAs? Result?

Assembly of new –RNAs: occurs during particle assembly

Replicase (RNA-dependent RNA Polymerase): synthesizes –RNA from +mRNAs, resulting in the formation of dsRNA genome segments

Rotavirus
Life Cycle

What does the newly synthesized capsid proteins enclose? Form? Final result?

Newly synthesized capsid proteins enclose dsRNA segments and viral enzymes: forms the immature virus particles; results in the eventual production of infectious virus particles that lyse the infected cell during egress.

Rotavirus
Laboratory Diagnosis

When in the disease process is the virus detected?
By what diagnostic tools (3)?

What is also used to detect virus infection?

Virus in stool collected early in the illness (detected by immune electron microscopy, ELISA or immunoassay)

Rise in titer of Ab to VP6 is also used to detect virus infection.

Immune Response to Rotavirus (3):

B cells (IgA and IgG) T cells (CD4) IFN

Prevention and Treatment of Rotavirus Infection Prevention: Vaccination: Treatment:

Waste-water treatment and sanitation. Two live (attenuated) oral vaccines available (85-98% effective) Replacement of fluids and restoration of electrolyte balance by IV or orally.

What is the most common cause of viral gastroenteritis in older children and adults?

Norovirus (Norwalk-like viruses)

Norwalk Virus Group: Family: Genus: Species:

Group: Group IV ((+)ssRNA) Family: Caliciviridae Genus: Norovirus Species: Norwalk virus

Norovirus (Norwalk-like Virus) Transmission: Common Age Groups: Incubation Period:

Transmission: fecal-oral; frequently associated with ingestion of contaminated foods (ie. shellfish) Common Age Groups: commonly affects older children and adults Incubation Period: 1 to 4 days

Norovirus (Norwalk-like Virus) Symptoms (5): Occur in what %? Similar to? Recovery time:

Chills, headache, myalgia, fever, N/V/D Occur in 25-50% of cases Similar to rotavirus Recovery in 24-48 hours

Norovirus (Norwalk-like Virus) ``` Basic properties: Genome type: What type of replicase enzyme? # of serotypes: Cultivatable? ```

Properties: Small, spherical particles +ssRNA genome Contains replicase enzyme (RNA-dependent RNA polymerase) At least 4 different serotypes Not cultivatable

Norovirus (Norwalk-like Virus) Immune Response Strain specific? Protection from Abs: Role of cell-mediated immunity:

Immunity is strain-specific Abs produced, but provide no long term protection (re-infection can occur) Role of cell-mediated immunity involves both CD4+ and CD8+ T-cells

Norovirus (Norwalk-like Virus) Prevention: Alcohol gels: Vaccine: Treatment:

Prevention. 1. Thorough and frequent hand washing with soap and water. 2. Alcohol based gels are NOT adequate. 3. 10% bleach required to clean surfaces. 4. No available vaccine Treatment. 1. Adequate hydration.

Norovirus (Norwalk-like Virus) Pathogenesis ``` More common what time of year? Transmission type: More common in what population? Particles sufficient for an infection: Stable? ```

"Winter vomiting disease": more common in winter Fecal-oral transmission: associated with ingestion of contaminated food, such as shellfish, and water. Common in older children and adults Highly contagious; 10-20 particles sufficient for infection Highly stable capsid protein. Can last on surfaces for days

Norovirus (Norwalk-like Virus) Pathogenesis ``` Incubation period: When is the patient highly infectious? Symptoms: 25-50% of cases involve: Recovery time: ```

Incubation period is 12-48 hours. Highly infection when symptoms appear to at least 3 days after symptoms disappear and may be shed 2 weeks after illness. Symptoms: abrupt onset of vomiting. Nausea, severe stomach cramps, and diarrhea. 25-50% of cases involve chills, headache, myalgia, or fever. Recovery occurs within 24-48 hours.