Viral Gastroenteritis Flashcards

1
Q

What is the definition of gastroenteritis?

A

Inflammation of the lining of the intestine, leading to diarrhea

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2
Q

When does gastroenteritis happen in the US, and what is the most common origin?

A

Happen during the winter months, especially in daycare centers, with an incubation period of 1-4 days.

More than half of cases of acute diarrheal disease are viral in origin.

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3
Q

What are the four families of viruses causing gastroenteritis, and what age groups do they typically infect?

A
  1. Reoviridae (respiratory and enteric orphan virus) = Rotavirus - young children, especially 6 mo. - 2 years.
  2. Adenovirus - children
  3. Calicivirus = Norovirus - all ages
  4. Astrovirus - Mild diarrhea in young children or elderly
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4
Q

What are the genomic structures of the major gastro-enteritis causing viruses?

A
  1. Rotavirus - dsRNA
  2. Adenovirus - dsDNA
  3. Calicivirus - ss+RNA
  4. Astrovirus - ss+RNA
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5
Q

What is the transmission pattern and site of infection for rotavirus?

A

Fecal-oral, with common nosocomial transmission

Site of infection: tip of villi of small intestine

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6
Q

What are the pathogenic mechanisms inducing diarrhea via Rotavirus?

A
  1. Direct cellular damage - damaging Na+ and glucosa absorption
  2. Activation of intestinal nerves - stimulation of enterocytes to secrete water

Leads to 10-20 diarrheal episodes per day with severe dehydration

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7
Q

What type of virus (structure) is rotavirus? How many proteins?

A

Non-enveloped, icosahedral with triple-layered protein capsid. Very ionically / pH / temperature stable.

dsRNA genome with 11 segments, encoding 12 proteins (6 structural, 6 nonstructural).

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8
Q

What is NSP4?

A

Non-structural protein 4

The first known viral enterotoxin which induces diarrhea

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9
Q

How does attachment and entry of rotavirus occur? (include two relevant proteins)

A

VP4 of viral capsid binds cellular sialic acid / integrins

During endocytosis, outer shell (VP7) is uncoated.

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10
Q

What is the function of the virion-associated Replicase?

A

It is an RNA-dependent RNA polymerase.

When the virus is in the lysosome, it uses the (-) strand of the dsRNA to synthesize more + strands, which are translated by the host cell.

During viral assembly in the viroplasm, new (-) strands are synthesized from + strands of RNA via the replicase.

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11
Q

What is the significance of using a replicase instead of host machinery to transcribe RNA?

A

prevents the host cell from seeing dsRNA, which would activate the antiviral mechanisms

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12
Q

What are two ways to detect rotavirus infection?

A

An ELISA (lateral flow assay) for the virions in the stool, or a serum rise in antibody titer to VP6 (coat protein beneath VP7)

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13
Q

What is the typical cause of Norovirus? (Calicivirus family)

A

Food-borne illness, with up to 20 million cases a year because it infects older children and adults, leading to hospital ward closures.

Happens in winter months most frequently

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14
Q

Why is it so easy to spread Norovirus?

A

You are still highly infectious even at least 3 days after symptoms disappear, and 10-20 viral particles is sufficient for infection. The capsule is similarly fastidious like Rotavirus.

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15
Q

How is genetic diversity generated in Norovirus?

A

It has a ss+RNA genome which is copied by the Replicase (RNA-dependent RNA polymerase), which is highly error prone

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16
Q

What is needed to prevent the virus?

A

Thorough handwashing with soap and water -> alcohol-based gel hand sanitizer will not kill it.

17
Q

What are the main clinical features of a hepatitis?

A

Inflammation and damage to the liver which causes liver enlargement, accompanied by jaundice, abdominal pain, and fever, with elevated ALT and AST

18
Q

What are the families of Hepatitis A-E? How do you remember the genome of C?

A
A: RNA picoRNAvirus
B: DNA hepaDNAvirus
C: RNA Flavivirus
D: RNA deltavirus
E: RNA hepevirus

Genome of C must be RNA due to the high antigenic variation

19
Q

Which hepatitis viruses are killed by the GI tract and which are stable?

A

Vowels hit your bowels - naked viruses are A and E which have fecal-oral transmission

20
Q

Where does Hep A typically replicate and how is it spread?

A

Replicates starting in intestinal mucosa then spreads to liver, with large amounts being excreted in feces (fecal-oral transmission)

Incubation is relatively short (about 1 month)

21
Q

What hepatitis viruses do we have vaccines for?

A

A, B, D (through B), and E

22
Q

What are the three B’s of Hep B spread? Who typically spreads it?

A

Blood, baby-making (sex), and birthing (perinatal)

Typically spread by asymptomatic carriers who do not express serum-sickness type syndrome (fever, arthralgias, rash)

23
Q

What is the incubation period of Hep B and what percentage of infected individuals will go on to develop chronic disease?

A

Long - 2-6 months

Only 5% will develop chronic or carrier state

24
Q

What does chronic HBV infection put you are risk for?

A

Poor 5-year survival of chronic active hepatitis, and increased risk of HCC (hepatocellular carcinoma)

25
Q

What are the three types of particles of HBV?

A
  1. Dane particles - mature and infectious DNA virion
  2. Sphere form - massively predominant, no genome and non-infectious
  3. Filamentous

Forms 2/3 are just the product of rapid nonselective viral replication

26
Q

What is the most diagnostic thing that shows the presence of a recent HBV infection? What is the critical period which we are covering for?

A

Presence of IgM antibodies to Hepatitis B core antigen (HBcAg)

Will persist even during the window period when HepB surface antigen (HBsAg) is not seen in the blood, and anti-HBsAg are not of protective, detectable titers

27
Q

What is HBsAg?

A

Hepatitis B surface antigen, expressed on all three viral forms. Finding this is definitely diagnostic of HBV infection

28
Q

What marker indicates are rapidly dividing and active HBV infection?

A

HBeAg - Hepatitis B early antigen. Shows the virus is very actively replicating. It is released from a virion core by a detergent treatment and is soluble in serum

29
Q

What is the viral genome of HBV?

A

A circular dsDNA, with a full length (-) strand and a partial length (+) strand of varying length.

30
Q

What is the mechanism of formation of mRNA in HBV viral replication cycle within hepatocytes?

A
  1. Enters the cell, is uncoating, and the partially dsDNA is converted into cccDNA (covalently closed circular form DNA) by host enzymes.
  2. Minus strand DNA is transmited into full length plus-strand RNA
31
Q

What happens in hepatocytes in HBV once viral mRNA has been synthesized?

A

P(olymerase) protein takes over -> a virally encoded DNA/RNA-dependent DNA polymerase.

Does act as a reverse transcriptase: It uses mRNA to synthesize full length (-) DNA.

It then uses the full length minus DNA to produce a partial (+) DNA for viral replication.

32
Q

How is HBV released?

A

The core acquires the HBsAG-containing envelope in the process of releasing from an infected cell.

33
Q

What type of vaccine is the HBV vaccine and how is it treated?

A

Recombinant (subcellular) vaccine

Treated via interferon-alpha or HBV polymerase (P protein) inhibitors.

34
Q

How does Hep D replicate and what is the one protein it encodes?

A

D = Defective = Depends on HBsAg for encapsulation

Encodes one protein via its ss-RNA genome = delta antigen, expressed in RNA encapsidation

35
Q

What is the primary pattern of Hep C transmission? What is its genome?

A

Blood: especially needles, syringes, and tattoos / body piercings

Genome is ssRNA

36
Q

Who is at greatest risk for fulminant disease in Hep E?

A

Hep E = Expectant mothers -> pregnant women have mortality rate of 20%

37
Q

What is interesting about Hep G?

A

It is correlated with slowed progression of HIV progression and prolonged survival in AIDS.