Mucosal RNA Viruses

Question 1

Mucosal viruses are defined as. . .

Answer 1

. . .viruses which infect the mucosal epithelium, but do not spread to the deeper tissues of the body.

Question 2

Rotaviruses

Answer 2

Mucosal RNA virus. Double stranded RNA genome. Name means “wheel” viruses, as they look like a wheel when segmented.

• Capsid provides acid stability that allows the virus to survive the stomach.
• Infect almost every child at some point (6 months - 2 years)

Question 3

Source of a rotavirus infection

Answer 3

• Person-to-person transmission
• Fecal-oral route
• Outbreaks usually due to municipal water contamination
• Transmission via food contamination is rare, but does occur

Question 4

Rotavirus-mediated disease

Answer 4

• May present as anything from asymptomatic to severe diarrhea
• Seasonal distribution; peaks in winter
• More servere cases in children 6-24 months of age
• 2 day incubation, vomitting for 2-3 days, then onset of diarrhea lasting 3-8 days
• Fever, abdominal cramps

Question 5

Rotavirus-mediated damage

Answer 5

• Infection induces gastroenteritis
• Infection associated with villus atrophy, denuded villi, mononuclear cell infiltration into lamina propria
• Immature enterocytes predominate (worse at regulating water level in gut, produce less disaccharides and ergo lower carbohydrate absorption)
• Rotavirus-derived enterotoxin causes chloride and water secretion
• Enteric nervous system activated to peristalse

Question 6

Diagnosis of rotavirus infection

Answer 6

• Does not grow well in cell culture
• Detection of viral antigen in stool works
• PCR is gold standard

Question 7

Rotavirus treatment and prevention

Answer 7

• No specific threatments for active infection
• Oral immunization with live, attenuated strain is recommended. Given between 6 and 14 weeks of age.

Question 8

Noroviruses

Answer 8

• Norwalk virus is the prototypical strain
• Mucosal RNA viruses

Question 9

Source of a norovirus infection

Answer 9

• Fecal-oral transmission is the primary route
• May be transmitted as an aerosol during episodes of vomitting
• Outbreaks relating to food and water common
• Asymptomatic infection is common
• Shedding may occur for 3 to 6 weeks even after recovery from illness
• Transmission from asymptomatic shedders is a very common way to be infected

Question 10

Norovirus-mediated disease

Answer 10

• Norovirus gastroenteritis is mild, lasts 24-48 hours (prolonged in immunocompromised patients, up to ~2 years)
• Nausea, abdominal cramps, vomitting, diarrhea, malaise
• Frequently occurs as an outbreak
• Peaks in winter
• Durable immune protection is not conferred by infection

Question 11

Norovirus-mediated damage

Answer 11

• Villus blunting in small intestine, but intestinal mucosa intact
• Gastric emptying delayed
• Malabsorption of fat, d-xylose, and lactose

Question 12

Diagnosis of norovirus

Answer 12

Identification of the viral RNA in stool by RT-PCR

Question 13

Treatment and prevention of norovirus

Answer 13

• No specific treatment options exist
• Hydrating, electrolyte replacement, IV fluids in extreme cases
• No proven vaccines

Question 14

Influenza virus

Answer 14

• Three types: A, B, and C. Type A has an animal reservoire, Type B and C are human specific.
• Consist of eight separate RNA segments encoding up to 12 proteins
• Each RNA segment coated by NP (viral nucleoprotein) and three polymerase proteins (PA, PB1, PB2). NP capsules are surrounded by M protein (matrix).
• Capsid surrounded by a host-derived envelope from which hemagglutinin (H) and neuraminidase (N) project.

Question 15

Influenza virus diagram

Answer 15

Question 16

Source of influenza infection

Answer 16

• Transmitted person-to-person by airborne droplets and by direct contact
• Coughing and sneezing aid spread
• Influenza A (but not B or C) may spread from pigs or birds to humans

Question 17

Influenza-mediated disease

Answer 17

• Incubation period of 1-2 days followed by 3-6 days of symptoms and shedding
• Onset of A or B: Abrupt headache, fever, chills, myalgia, cough, sore throat, malaise
• Complications of A or B: Usually uncomplicated, may result in bacterial pneumonia or rarely viral pneumonia due to immunocompromisation
• Onset of C: Nonseasonal, usually occur in children ages 1-4.

Question 18

Influenza-mediated damage

Answer 18

• Infects mucosa of respiratory tract (ciliated and nonciliated epithelium)
• Induces edema and monocytic inflammation in uncomplicated cases
• In severe cases, necrotizing tracheobronchitis and bronchiolitis may occur
• Fibrosis induced by chronic inflammatory response may lead to respiratory issues
• Loss of ciliated cells along epithelium during influenza infection is what is thought to lead to the associated bacterial pneumonia susceptibility

Question 19

Infection of cells by influenza viruses is initiated by attachment of ___ to ___.

Answer 19

Infection of cells by influenza viruses is initiated by attachment of hemagglutinin to sialic acid.

Question 20

Role of M2 protein in infleunza

Answer 20

A channel that allows hydrogen ions to pass through the capsid into the core. This initiates the uncoating of the viral capsid, the internal proteins, and the RNA.

Question 21

Amantadine and Rimantadine

Answer 21

Antivirals which inhibit the uncoating of infleunza proteins by blocking the M2 channel in the influenza capsid.

Question 22

“Cap snatching” oberved in influenza

Answer 22

Viral RNA-dependent RNA polymerase cleaves the 5’ cap from nascent host RNAs and uses it to prime its own synthesis.

Question 23

Baloxavir marboxil

Answer 23

Antiviral which blocks the cap-dependent endonuclease activity of the influenza RNA-dependent RNA polymerase

Question 24

Function of influenza neuraminidase

Answer 24

Cleaves all of the sialic acid residues as influenza virions are budding from a host cell in order to prevent re-entry into that cell or virion-virion fusion.

Question 25

Oseltamivir and Zanamivir

Answer 25

Antivirals which prevent removal of host sialic acid by neuraminidase, causing virions to fuse to one another and inhibiting their ability to affect new cells.

Question 26

Genome reassortment in influenza

Answer 26

May occur when two strains of influenza infect the same cell. Since each RNA is packaged individually, if two infleunzas are in the same cell at the same time, they can trade genetic information, enabling horizontal gene transfer between viral strains.

Question 27

Epidemiology of Influenza

Answer 27

Annual outbreaks of influenza are **epidemics.** These occur in the winter in temperate climates. Antibodies against HA and NA are the main forms of host defense, however these proteins mutate frequently and may be traded between strains. A **pandemic** is an explosive, world-wide epidemic. Very irregular, ~3 per century. **Pandemics are caused by Type A Infleunza**, typically aquired from another animal species with an H/N antigen that human populations have not seen and may not have MHC to target.

Question 28

H/N Subtypes of Infleunza A

Answer 28

Only Infleunza A has subtypes There are 16 H subtypes and 9 N subtypes, with little to no cross-reactivity.

Question 29

In a typical year, ____ strains of influenza will circulate.

Answer 29

In a typical year, **two to four** strains of influenza will circulate. **one or two Type A** **one or two Type B**

Question 30

Diagnosis of Influenza

Answer 30

May be done by immunological methods (H/N typing) or RT-PCR. RT-PCR is more sensitive.

Question 31

Treatment and Prevention of Influenza

Answer 31

* Antivirals may be used to treat symptoms. They are most effective when given early and may be given prophylactically to those in close proximity. * Vaccines are made every year based on what subtypes are expected to circulate, however the coverage varries from year to year based on how good the prediction was * 50-60% effective vaccines if predictions are good *

Question 32

Adamantanes are only effective against. . .

Answer 32

Type A Influenza

Question 33

Types of flu vaccine

Answer 33

Question 34

What step in replication of influenza B viruses can be directly inhibited by an antiviral drug that is currently in use?

Answer 34

Release of virus from the infected cell. These would be neuraminidase inhibitors. Adamantanes, which block the M2 channel, work for Influenza A but not B.

Question 35

\_\_\_\_ viruses tend to be less stable under harsh environmental conditions, such as low pH.

Answer 35

**Enveloped** viruses tend to be less stable under harsh environmental conditions, such as low pH. This is why enveloped viruses cannot usually pass through the stomach into the GI tract.

Question 36

Antigenic drift of influenza viruses is primarily a result of their. . .

Answer 36

low-fidelity RNA-dependent RNA polymerases

Question 37

\_\_\_ seems to be associated with mucosal-limited replication.

Answer 37

**Poor long-term immunity** seems to be associated with mucosal-limited replication.

Question 38

Norovirus does not have an associated. . .

Answer 38

. . . enterotoxin. It achieves its secretory diarrhea effect simply by killing mature enterocytes and preventing good reabsorption.

Question 39

Influenza-like illness

Answer 39

Acute fever + One or both of: cough / sore throat

Question 40

Reassortment

Answer 40

Exchange of information in viruses, specifically segmented RNA viruses