Disseminating RNA Viruses I

Question 1

Arboviruses

Answer 1

Arthropod borne-viruses. Tranmitted by insects, usually ticks, mosquitoes, blood feeding flies, etc. Replicate within host then spread to salivary glands. For most arboviruses, humans are dead-end hosts, while amplifying infections occur in birds or smaller mammals.

Question 2

Arboviruses for which humans are not dead-end hosts

Answer 2

Yellow fever and dengue

Question 3

Arbovirus transmission cycle

Answer 3

Question 4

Three major manifestations of human arbovirus infection

Answer 4

1. Meningitis or meningoencephalitis (CNS inflammation)
2. Hepatitis (especially yellow fever)
3. Hemorrhagic fever

Question 5

Hemorrhagic fever

Answer 5

Infection where damage is particularly severe to the small blood vessels, with hemorrhage in the skin (forming petechiae) and within organs.

Question 6

Petechiae

Answer 6

Question 7

West Nile Virus

Answer 7

A type of falvivirus: +ssRNA, enveloped. Inside the envelope are C (capsid) and M (matrix) proteins. Increasingly prevalent in the Western hemisphere.

Question 8

Source of West Nile virus infection

Answer 8

Transmitted by mosquitoes. Transmission via blood transfusion, breast milk, or organ transplant also possible.

Question 9

West Nile Virus-mediated disease

Answer 9

• 8/10 do not develop symptoms
• 2/10 develop fever with headaches, body aches, joint pain, vomitting, diarrhea, rash, and fatigue. Most recover completely, but fatigue lasts for ~2 weeks longer after other syptoms resolve.
• 1/150 develop meningitis or encephalitis. Symptoms include high fever, headache, neck stiffness, stupor, disorientation, coma, tremors, vision loss, weakness, numbness, paralysis. Elderly and immunocompromised at increased risk. Recovery takes weeks to months, some CNS effects may be permanent. Mortality rate of 10%

Question 10

West Nile Virus-mediated damage

Answer 10

Mosquito saliva contains virions which infect skin keratinocytes or langerhans cells. Infected keratinocytes or DCs migrate to draining lymph node, where serum viremia is geneated. Capable of accessing and eliciting pathology in the brain.

Question 11

Ways West Nile Virus may infect the nervous system

Answer 11

1. Crossing blood-brain barrier due to cytokine-mediated permeability of blood vessels
2. Infection of the endothelium of the blood brain barrier
3. Infecting tissue macrophages which are trafficked across the blood brain barrier
4. Retrograde axonal transport from peripheral neurons to cell bodies in the CNS

Question 12

Treatment and prevention of West Nile Virus

Answer 12

There are no antivirals effective against WNV.

There are no vaccines for WNV.

Question 13

Hepatitis Viruses

Answer 13

“Professional” hepatitis viruses, which have a strong tropism for hepatocytes and preferentially replicate there. There are 5, A-E, and they are defined by their ability to infect the liver preferentially, not their relatedness.

• A and E are acquired by ingestion. Both are cleared readily by healthy immune systems and so are usually transient.
• B and C may be transmitted percutaneously, sexually, or vertically. These are difficult to eliminate and often result in chronic infection.
• D is not a “true virus,” but a subviral agent incapable of disseminating and replicating without B. Co-infection with Hep B and D makes cases much worse and more complicated.

Question 14

Hepatitis A through D virus summary

Answer 14

Question 15

Hepatitis A

Answer 15

Nonenveloped, +ssRNA virus, picornaviridae family.

Acquired from ingestion, usually causes transient infection resulting in hepatitis. May also appear transiently in the bloodstream, which may result in contagion via blood.

Question 16

Hepatitis A-mediated damage

Answer 16

Absorbed in the intestine and travels via portal system to the liver. Infects hepatocytes. Newly syntesized particles are excreted into bile ducts.

Infection of hepatocytes impairs normal hepatocyte functions, leading to bilirubin buildup (jaundice), fever, abdominal pain, nausea, vomitting, and pale feces (due to lack of pigment).

In more servere cases, mental function is impaired due to toxins from the GI tract that are not being cleared by the liver as they normally would. Hemophilia may result from lack of sufficient clotting factor production.

Question 17

Poop color chart

Answer 17

Question 18

Typical course of acute hepatitis A infection (graph)

Answer 18

Question 19

Treatment and Prevention of Hepatitis A

Answer 19

There are no antivirals to treat Hepatitis A. However, those exposed may be treated with antiserum to reduce extent and severity (postexposure prophylaxis).

There is a vaccine against Hep A which is safe, highly immunogenic, and highly effective. Vaccination now recommended for all in the US.

Question 20

Hepatitis A epidemiology

Answer 20

Very common in endemic areas with low sanitation. Most children infected in first few years of life, largely unaffected, and later immune.

Adults from non-endemic regions are more likely to display symptoms, although death is rare. HAV does not cause chronic or persistent infections, and after infection the host is almost always immune to subsequent infections.

Question 21

What may be used to diagnose Hepatitis A infection

Answer 21

ELISA for antiviral serum IgM

Question 22

The first round of WNV replication is. . .

Answer 22

. . .at the site of the mosquito bite.

From here, they expand until they infect langerhans cells and get into the lymph.

Question 24

___ and ___ are viruses which spread up axons via retrograde transport to the CNS.

Answer 24

Herpes virus and rabies are viruses which spread up axons via retrograde transport to the CNS.

Question 25

By the time a patient for WNV develops neuroinvasive disease, there is usually. . .

Answer 25

. . . little to no virus in the CSF. This makes CSF RT-PCR a poor diagnostic technique for WNV.

Question 26

Hep A virions are very \_\_\_.

Answer 26

Hep A virions are very **stable**. They may last for up to months and may survive freezing.

Question 27

Current postexposure prophylaxis protocol for Hep A

Answer 27

1. Immunization (if not already) with Hep A vaccine 2. IVIG if indicated