Viral Gastroenteritis Flashcards
What is the definition of gastroenteritis?
Inflammation of the lining of the intestine, leading to diarrhea
When does gastroenteritis happen in the US, and what is the most common origin?
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.
What are the four families of viruses causing gastroenteritis, and what age groups do they typically infect?
- Reoviridae (respiratory and enteric orphan virus) = Rotavirus - young children, especially 6 mo. - 2 years.
- Adenovirus - children
- Calicivirus = Norovirus - all ages
- Astrovirus - Mild diarrhea in young children or elderly
What are the genomic structures of the major gastro-enteritis causing viruses?
- Rotavirus - dsRNA
- Adenovirus - dsDNA
- Calicivirus - ss+RNA
- Astrovirus - ss+RNA
What is the transmission pattern and site of infection for rotavirus?
Fecal-oral, with common nosocomial transmission
Site of infection: tip of villi of small intestine
What are the pathogenic mechanisms inducing diarrhea via Rotavirus?
- Direct cellular damage - damaging Na+ and glucosa absorption
- Activation of intestinal nerves - stimulation of enterocytes to secrete water
Leads to 10-20 diarrheal episodes per day with severe dehydration
What type of virus (structure) is rotavirus? How many proteins?
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).
What is NSP4?
Non-structural protein 4
The first known viral enterotoxin which induces diarrhea
How does attachment and entry of rotavirus occur? (include two relevant proteins)
VP4 of viral capsid binds cellular sialic acid / integrins
During endocytosis, outer shell (VP7) is uncoated.
What is the function of the virion-associated Replicase?
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.
What is the significance of using a replicase instead of host machinery to transcribe RNA?
prevents the host cell from seeing dsRNA, which would activate the antiviral mechanisms
What are two ways to detect rotavirus infection?
An ELISA (lateral flow assay) for the virions in the stool, or a serum rise in antibody titer to VP6 (coat protein beneath VP7)
What is the typical cause of Norovirus? (Calicivirus family)
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
Why is it so easy to spread Norovirus?
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.
How is genetic diversity generated in Norovirus?
It has a ss+RNA genome which is copied by the Replicase (RNA-dependent RNA polymerase), which is highly error prone
What is needed to prevent the virus?
Thorough handwashing with soap and water -> alcohol-based gel hand sanitizer will not kill it.
What are the main clinical features of a hepatitis?
Inflammation and damage to the liver which causes liver enlargement, accompanied by jaundice, abdominal pain, and fever, with elevated ALT and AST
What are the families of Hepatitis A-E? How do you remember the genome of C?
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
Which hepatitis viruses are killed by the GI tract and which are stable?
Vowels hit your bowels - naked viruses are A and E which have fecal-oral transmission
Where does Hep A typically replicate and how is it spread?
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)
What hepatitis viruses do we have vaccines for?
A, B, D (through B), and E
What are the three B’s of Hep B spread? Who typically spreads it?
Blood, baby-making (sex), and birthing (perinatal)
Typically spread by asymptomatic carriers who do not express serum-sickness type syndrome (fever, arthralgias, rash)
What is the incubation period of Hep B and what percentage of infected individuals will go on to develop chronic disease?
Long - 2-6 months
Only 5% will develop chronic or carrier state
What does chronic HBV infection put you are risk for?
Poor 5-year survival of chronic active hepatitis, and increased risk of HCC (hepatocellular carcinoma)
What are the three types of particles of HBV?
- Dane particles - mature and infectious DNA virion
- Sphere form - massively predominant, no genome and non-infectious
- Filamentous
Forms 2/3 are just the product of rapid nonselective viral replication
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?
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
What is HBsAg?
Hepatitis B surface antigen, expressed on all three viral forms. Finding this is definitely diagnostic of HBV infection
What marker indicates are rapidly dividing and active HBV infection?
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
What is the viral genome of HBV?
A circular dsDNA, with a full length (-) strand and a partial length (+) strand of varying length.
What is the mechanism of formation of mRNA in HBV viral replication cycle within hepatocytes?
- Enters the cell, is uncoating, and the partially dsDNA is converted into cccDNA (covalently closed circular form DNA) by host enzymes.
- Minus strand DNA is transmited into full length plus-strand RNA
What happens in hepatocytes in HBV once viral mRNA has been synthesized?
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.
How is HBV released?
The core acquires the HBsAG-containing envelope in the process of releasing from an infected cell.
What type of vaccine is the HBV vaccine and how is it treated?
Recombinant (subcellular) vaccine
Treated via interferon-alpha or HBV polymerase (P protein) inhibitors.
How does Hep D replicate and what is the one protein it encodes?
D = Defective = Depends on HBsAg for encapsulation
Encodes one protein via its ss-RNA genome = delta antigen, expressed in RNA encapsidation
What is the primary pattern of Hep C transmission? What is its genome?
Blood: especially needles, syringes, and tattoos / body piercings
Genome is ssRNA
Who is at greatest risk for fulminant disease in Hep E?
Hep E = Expectant mothers -> pregnant women have mortality rate of 20%
What is interesting about Hep G?
It is correlated with slowed progression of HIV progression and prolonged survival in AIDS.
