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1) Which of the following diseases is caused by a member of the flavivirus family?
a) Yellow Fever
b) Dengue Fever
c) West Nile Encephalitis
d) Hepatitis C
e) All of the above.
e) All of the above.
2) Which of the following describes the primary mechanism of transmission of the flavivirus Hepatitis C?
a) Mosquito bites
b) Contaminated blood transfusions
c) Aerosols
d) Contaminated food and water
e) Animal bites
b) Contaminated blood transfusions
3) How was Yellow Fever Virus introduced into the New World from Africa?
a) Infected animals were imported.
b) Tires containing infected mosquitoes were imported.
c) Migrating birds brought it.
d) It came over on slave trading ships.
e) Walter Reed released it from a laboratory.
d) It came over on slave trading ships.
4) The yellow fever vaccine strain has 32 amino acid mutations in comparison to the wildtype pathogenic virus strain. Which of the following genes contains the majority of these amino acid substitutions?
a) Polymerase
b) Capsid protein
c) Envelope glycoprotein
d) Protease
e) Helicase
c) Envelope glycoprotein
5) Which of the following techniques was used to isolate the flavivirus Hepatitis C virus?
a) Molecular cloning of the viral cDNA
b) Purification of virus particles
c) Antibody staining with patient serum
d) Plaque assay
e) Southern blotting
a) Molecular cloning of the viral cDNA
6) In the mature flavivirus virion, the fusion peptide on the E protein is buried in the dimer interface. Which of the following conditions causes the fusion peptide to become exposed?
a) Uptake of the virion via receptor mediated endocytosis.
b) Interaction with the sialic acid residues on the surface of the cell.
c) Binding to the host cell receptor on the surface of the cell.
d) Drop in pH in the endosome.
e) Binding to the host cell membrane.
d) Drop in pH in the endosome.
7) The hydrophobic region of the flavivirus capsid protein is thought to do which of the following?
a) Bind to the host cell receptor.
b) Interact with the viral envelope.
c) Insert into the host cell membrane.
d) Interact with and condense the genomic RNA.
e) Bind to other capsid proteins.
b) Interact with the viral envelope.
8) Which of the following describes the phenomenon of antibody-dependent enhancement?
a) Antibodies bound to a flavivirus particle allows entry into a cell via the Fc receptor.
b) Antibodies bound to the host cell receptor make it unable to bind a flavivirus particle.
c) Antibodies bound to infected cells cause the immune system to kill them.
d) Antibodies bound to a flavivirus particle allow it to be removed by the immune system.
e) The overproduction of antibodies during a flavivirus infection
a) Antibodies bound to a flavivirus particle allows entry into a cell via the Fc receptor.
9) Which of the following conditions is required to induce fusion of the flavivirus envelope with the host cell membrane?
a) Increase in pH
b) Decrease in pH
c) Binding of envelope protein to the host cell receptor
d) Uptake of the virion into a vesicle.
e) Proteolytic degradation of the virion.
b) Decrease in pH
10) Which of the following statements comparing flaviviruses with togaviruses is FALSE?
a) Flaviviruses have a T=3 capsid while togaviruses have a T=4 capsid.
b) Flaviviruses have smaller virions that togaviruses.
c) Flaviviruses do not produce subgenomic RNAs like togaviruses.
d) Flaviviruses have enveloped virions but togaviruses have naked virions.
e) Flaviviruses produce a single-polyprotein while togaviruses produce more than one.
d) Flaviviruses have enveloped virions but togaviruses have naked virions.
11) Which of the following statements comparing flaviviruses with picornaviruses is FALSE?
a) They both use an IRES to initiation translation of the viral genome.
b) They both have enveloped virions
c) They both encode the structural proteins at the 5’ end of the genome.
d) They both produce their proteins from a single open-reading frame.
e) They both produce viral proteases to cleave the polyprotein.
b) They both have enveloped virions
12) The nonstructural proteins of flaviviruses are produced on the rough ER and have membrane spanning domains. Which of the following explains why the nonstructural proteins are localized to cellular membranes?
a) Fatty acids are a required cofactor for RNA synthesis.
b) Viral RNA replication can only occur in the lumen of the ER.
c) Membranes serve to localize the viral replication complex.
d) The viral replication proteins must be glycosylated before they are active.
e) The nonstructural proteins require proteolytic processing by lysosomal enzymes.
c) Membranes serve to localize the viral replication complex.
13) Flavivirus virions obtain their envelopes from the cellular membranes of which of the following organelles?
a) Endoplasmic Reticulum
b) Nucleus
c) Golgi apparatus
d) Plasma membrane
e) Mitochondria
a) Endoplasmic Reticulum
14) Which of the following proteins from flaviviruses has the RNA-dependent RNA polymerase activity?
a) NS1
b) NS2
c) NS3
d) NS4
e) NS5
e) NS5
15) Which of the following cellular proteases helps to process the polyprotein of flaviviruses?
a) Chymotrypsin
b) Trypsin
c) Furin
d) Cathepsin D
e) Papain
c) Furin
16) When is the “pr” region cleaved by the protease furin from the prM protein of flaviviruses?
a) During translation of the structural proteins.
b) When the virion acquires the envelope from the ER.
c) As the capsid is being assembled in the cytoplasm.
d) After the virion moves through the trans Golgi network.
e) After release of the virions from the host cell.
d) After the virion moves through the trans Golgi network.
17) West Nile Virus was introduced into the United States in 1999 and became an endemic infection over the next several years. Which of the following wild animal populations does this virus circulate in?
a) Bats
b) Bees
c) Birds
d) Beetles
e) Bears
c) Birds
18) Which of the following describes the reason why the precursor to the capsid protein from flaviviruses has a membrane spanning domain?
a) So that it is localized on the membranes where viral RNA replication takes place.
b) So that it islocalized on the membranes where the virions obtain their envelope.
c) So that it is close to where the other structural proteins are localized.
d) So that it will be translated by ribosomes associated with the ER.
e) All of the above are correct.
e) All of the above are correct.
19) A cloned DNA copy of the yellow fever virus can be used to produce infectious viral RNA.
TRUE
20) Infection with a second strain of Dengue fever virus within two years of having had the first strain causes Dengue Hemorrhagic Fever.
TRUE
21) Since flaviviruses replicate in the cytoplasm of the host cell, they do not need to encode a methyltransferase enzyme to produce the 5’ cap on the viral genomic RNA.
FALSE
22) In a flavivirus infection, newly synthesized positive-strand RNA genomes can only be packaged into new virions.
FALSE
23) Once the West Nile Virus became endemic in the United States, 20% of the population has seroconverted to the virus.
FALSE
24) Describe the events that events that lead West Nile virus from moving from a local epidemic to becoming endemic in the United States.
Answer: West Nile virus was originally isolated from Uganda and is found in several parts of the world including the Middle East, Europe and Asia. The first outbreaks of West Nile Virus in the US were in the New York City region in 1999 when dead birds were seen in high numbers. Over the course of the next several years, the virus moved westward eventually causing infections in birds and human in all 48 contiguous states. An increase in the mosquito population was thought to have enhanced the movement of West Nile across the country. The number of people exposed and infected with West Nile appears to have leveled off, though an increase in either infected mosquitoes or birds could lead to sporadic regional outbreaks.
25) Describe the final processing steps that the flavivirus virion goes through in order to be converted from an immature virion into a mature infectious virion.
Answer: The nucleocapsid buds into the lumen of the ER to obtain the envelope. The immature virion then progresses through the exocytosis pathway to eventually be released from the host cell. Movement of the virion through the low pH environment of the trans Golgi network causes the surface proteins of the virion to fold down into the flattened structure and exposes the furin cleavage site. This allows furin to cleave the prM protein into the final M protein. However, the “pr” peptide is not released from the virion until after the virion leaves the cell and is exposed to the neutral pH outside the host cell.