Flaviviruses Flashcards
Where was yellow fever most prevalent
when the panama canal was getting constructed
How was yellow fever transmitetd
by mosquities
aedes egypti
how did people discover how yellow fever was getting transmitted
they recruited volunteers and paid them
what is the type of virus of yellow fever
flaviviruses
What put an end to human experiments
clara maass a nurse that got paid for be bitted by yellow fever mosquitoes and she got killed
Mosquito brigades
- Colonel Gorgas arrived in Panama as the Chief Medical Officer (1904)
- Discoveries linking mosquitos with malaria
- Decides to act on possibility that insects could be transmitting yellow fever
- In 1905: “mosquito brigades”
-campaign to fumigate and eradicate the disease - By Aug 1906, there were just 7 cases of yellow fever along the Panama canal
Control of yellow fever
In 1915, the Rockefeller Foundation funded a project to eliminate breeding places for Aedes aegypti in areas where yellow fever was prevalent
why was yellow fever nor eradicated?
-transmission cycle is complicated
-humans get the disease from mosquitoes
-there is a third reservoir: monkeys
facts about the flaviviridae family
- Flavus (Latin = yellow)
- type virus: YFV
- Enveloped viruses
- Icosahedral capsid
- 40-60 nm in diameter
- Genome: (+) ssRNA
- monopartite, linear
- 9.6 -12.3 kb in length
JEV is part of which virus fam
flaviviridae
true or false: JEV is transmitted by mosquitoes
true
Hosts of JEV
- Primary hosts: birds, pigs
- Incidental/dead-end hosts: humans
Symptoms of JEV
- Symptoms: fever, headache, vomiting,
neurologic symptoms (mental status,
movement disorders, etc)
true or false: there is a vaccine for JEV
true
Encephalitis Viruses facts
- Majority are asymptomatic or cause
nonspecific febrile illness - Primarily affects children or young adults
(0-15 yrs old) but west nile is older people - More severe cases:
- Meningoencephalitis
- Aseptic meningitis
- Polio-like acute flaccid paralysis
- “Parkinsonian” syndromes (tremor,
cogwheel rigidity, masklike facies)
how can you get west nile
culex mosquitos
host of west nile
- Primary hosts: birds
- Incidental/dead-end hosts: humans, other
mammals
who gets west nile virus
Primarily elderly/immunocompromised
symptoms of west nile virus
Symptoms: fever, headache, vomiting, muscle
weakness, lower back pain, neurologic symptoms (loss
of motor function, encephalitis, meningitis)
true or false: the is no vaccine for west Nile virus
true
true or false: most of the cases of west nile are symptomatic
false they are mostly asymptomatic
How can you get dengue
Arbovirus, transmitted by
Aedes mosquitos (Aedes
aegypti and Aedes albopictus)
What are the primary host of dengue
human
symptoms of dengue
Fever, headache,
vomiting, abdominal pain, low
blood pressure, tachycardia,
seizures, encephalitis
True or false: there are no vaccines for dengue
true
True or false: mostly kids get dengue
false there is no age distingtion
How many subtypes of dengue are there and how are they spreaded our
there are four and they are all spreaded out over the world
where is zika the most prevalent?
in south america
how is zika spreaded
Arbovirus, transmitted by Aedes
mosquitos (primarily Aedes
aegypti)
What are the symptoms of zika
Symptoms (20%): fever,
maculopapular rash, headache,
joint and muscle plain, edema,
vomiting
when was the last outbreak of zika and what happenend
Recent outbreaks (2013-
Present): Guillain-Barré
syndrome and fetal
microcephaly
True or false: there is no vaccine for zika
true
what are the necessities to tackle an emerging virus
-model systems
-diagnostics
-vector control
-therapeutic strategies
true or false: flavivirus encode for a polyproteins
true
which +ssrna virus had an immature and a mature configuration
flavivirus
Virus entry: flavivirus
- E protein mediates attachment to receptor
- in late endosome, low pH —> E protein
conformational change - sticks into endosomal membrane
- results in fusion
What does facilitate flavivirus replications
genome circularizatio
what is the ration of + and - strand during replication?
there is always more + strands that are being made than - strands
Flavivirus replication results in sfrnas
- produced by XRN1 stalling on RNA knots in 3’UTR
- inhibit antiviral responses in both hosts
- type I IFN response in mammals
- RNAi pathway in mosquitos
- modulate cytopathic effects and cell death in mammals
what is srn-1
host exonuclease that degrades uncapped RNA
How did flaviviruses have to adapt to 2 hosts
- ie. conserved deletions in DENV 3’UTR upon mosquito- adaptation
- disrupts one of the XRN1- resistant structures
- leads to different primary sfRNA species
- increased fitness in mosquitos, reduced in humans
- reversion of deletions when re-adapted to humans
Infection involves a diverse population of viruses: flavivirus mutations
-the virus mutates a lot
* flavivirus RdRp’s introduce 1 mutation per new strand on average
* each new host/tissue/cell type will create different
selective pressures
* ie. in mosquitos:
* virus must first escape gut
* virus must eventually enter
salivary glands
True or false: flavivirus replication induces vps and cms
- DENV induces rough-ER- derived vesicle packets
(VPs) and convoluted membranes (CMs) - Sites of replication
- Vesicles have pores (presumed exit site for
newly synthesized viral RNAs)
Flavivirus assembly sites
- Budding viruses can be observed next to the
pores of VPs - Virions stack within the lumen of the VP- containing ER network
- Virions egress through the Golgi
how does flavivirus matures
the host furin will cleave the PrM into the M protein so that it is able to fuse with the host membrane
DENV Antibody-dependent Enhancement
- Increased severity of secondary infections
- Antibodies from 1º infection recognize different
serotypes weakly and facilitate DENV binding and internalization - Leukocytes and BBB cells (= encephalitis)
- Inflammation and cytokine secretion (cytokine storm)
- Compromises CNS function
