Hemorrhagic Viruses

Question 1

What are the main viruses in the Flavaviridae family?

Answer 1

Yellow fever

Dengue fever

Question 2

What are the main viruses in the Bunyaviridae family?

Answer 2

Rift Valley fever
Congo-Crimean HF
Hantavirus HF

Question 3

What are the main viruses in the Filoviridae family?

Answer 3

Ebola virus

Marburg virus

Question 4

What are the main viruses in the Arenaviridae family?

Answer 4

Lassa fever

South American fevers

Question 5

Describe the RNA for the following viral families:
Flavaviridae
Bunyaviridae
Arenaviridae
Filoviridae

Answer 5

Flavaviridae: +RNA
Bunyaviridae: -RNA
Arenaviridae: Ambisense RNA
Filoviridae: -RNA

Question 6

Describe the transmission vector for the following viral families:
Flavaviridae
Bunyaviridae
Arenaviridae
Filoviridae

Answer 6

Flavaviridae: mosquitos
Bunyaviridae:
RVF-mosquitos
C-CHF: ticks
HHF: rodent excreta
Arenaviridae: rodent excreta (including aersolized urine)
Filoviridae: bodily fluids (fruit bats are reservoir; fomite transmission also possible)

Question 7

Describe the pathogenesis of flaviviridae viruses.

Answer 7

human gets bit by mosquito, the virus starts replicating in epithelial/endothelial cells, this is where the disease course may stop but if it gets passed the immune system control then it will go to replicate in macrophages, liver, spleen, at this point it may cause severe systemic disease (HF, shock syndrome)

Question 8

Describe the symptoms and disease course of rift valley virus.

Answer 8

flu-like sx plus fever, encepahlitis, retinal vasculitis (may lead to blindness); may be mistaken for bacterial meningitis. 2% of cases progress to hemorrhagic hepatitis.

Question 9

Describe the pathogenesis and symptoms of dengue fever.

Answer 9

flu-like sx plus “bonebreak fever” - severe bone/muscle pain, frontal headache, metallic taste, mottled rash. Can progress to Dengue Shock Syndrome.

Question 10

Describe the symptoms of Hantavirus HF.

Answer 10

from rodent excreta, targets liver and vascular endothelium; causes fever, hemorrhage, and acute renal failure; >15% mortality

Question 11

Describe the symptoms of congo-crimean HF.

Answer 11

spread by ticks and target liver and vascular endothelium; causes outward hemorrhaging through skin and orifices, also causes headache and limb pain; clinical disease is rare but is severe in infected humans and has a 30% mortality

Question 12

Describe the symptoms of the arenaviridae.

Answer 12

begins insidiously with flu-like symptoms including fever, HA, malaise, joint pain, cough; severe multisystem organ disease occurs in 5-10%; may progress to severe case and may include prostration, dehydration, abdominal pain, facial/neck edema. Also seen are lymphopenia and thrombocytopenia/defective platelet function.

Question 13

Describe the symptoms of ebola.

Answer 13

rapid onset of flu-like symptoms; unless viral replication is halted will progress to hemorrhagic shock syndrome; highly fatal due to hypovolemic shock and multisystem organ failure

Question 14

Describe the symptoms of yellow fever.

Answer 14

flu-like symptoms, 15% of cases progress to more severe infection which consists of jaundice (from viral-mediated liver damage) and “black vomit” from GI diathesis/gastric mucosal hemorrhage; when progressed to hepatorenal disease there is a 20-50% mortality rate

Question 15

Which of the hemorrhagic viruses have a vaccine available?

Answer 15

yellow fever - live attentuated
rift valley fever - mostly only for animals because causes bad human side effects
*vaccines currently being tested for Filoviridae/Ebola

Question 16

Which of the hemorrhagic virus families has an ambisense RNA genome?

Answer 16

Arenaviridae

Question 17

____ has been shown to reduce the severity of illness caused by
arenaviruses producing hemorrhagic fever.

Answer 17

Intravenous ribavirin

Question 18

Describe the pathology of the filovirus-induced hemorrhagic fevers.

Answer 18

not well understood yet; macrophages/monocytes become infected and virus interferes with cytokine regulation, inducing a cytokine storm; viremia results in dissemination to live/kidney/spleen where high-level virus production ensues. Loss of platelets/immune cells results in coagulation and vascular abnormalities–hence hemorrhage–which causes swelling, organ damage/failure, and hypovolemic shock

Question 19

What’s the major stumbling block to creating a vaccine for the Dengue fever virus?

Answer 19

DV has four serotypes, where infection with one exacerbates disease following infection with a different serotype

Question 20

Is yellow fever able to be transmitted through fluids of infected individuals?

Answer 20

no - only mosquitos

Question 21

When is a person infected with filovirus contagious?

Answer 21

when they are symptomatic

Question 22

What is the current method for confirming diagnosis of ebola?

Answer 22

reverse transcription PCR (RT-PCR)

Question 23

Describe the process, including time window, for ebola testing and confirmation of diagnosis.

Answer 23

collect blood and run RT-PCR; if positive then it confirms the presence of ebola virus.
Note: if the blood is collected less than 72hrs post-symptom onset, a negative result does not necessarily rule out ebola infection; repeat testing after 72hrs if symptoms are still present

Question 24

Describe the process of viral entry and replication within a cell, from entry to release, including genome replication and protein synthesis steps/locations.

Answer 24

1. attachment, entry by endocytosis
2. pH-dependent fusion/uncoating
   3a. if -RNA, will first transcribe to +RNA
   3b. +RNA translated to proteins
   4a. viral RNA polymerase replicated genome
   4b. -RNA viruses use a +cRNA intermediate to replicate the -RNA genome
3. assembly of virion, budding to release from the cell

Question 25

For severe disease manifestation of the flaviviruses (including organ failure), what viremic process must occur?

Answer 25

a secondary viremia (escaping first response of immune system: the neutralizing antobody) following replication in the vascular endothelium must occur to seed the target organs