Exam3Lec3Arbobiruses/EmergingViralInfections Flashcards
Explain the emergence of urban transmission of flaviviruses
- Spillover from enzootic cycle: There is a virus that is normally contained in an ecosytem and there is a cycle of non-human primates gets infected by mosquito and primates infecting mosquito. Human gets exposed to virus by getting bitten by mosquito in foreign ecosystem.
- Human Urban Amplification: Human travels back to their home and passes it on to other vectors and human. There is interinfection between human infecting mosquito and mosquito infecting human
- Spillback into enzootic cycle: Humans travels back to ecosystem with a modified virus and brings it back inot the ecosystem.
Basic info about flavi viruses
rna (+) ss, icosahedral, cytoplasmic replication
flavi virusews are arboviruses meaning that they are arthropod-borne viruses, We get bitten by mosquitos or ticks
What are 5 arboviruses we see in FL?
- Dengue
- West nile
- Zika
- Chikungunya
- EEE
Did we have any human cases this year for Chikungunya in FL?
NO
For Dengue virus cases, how may importations and locally acquired in FL?
639 importation and 36 locally acquored. 92% importations from cuba (~60% DEN3 serotype)
cases go up every yr and they come from Cuba
What is the vector of flavivirus?
Arthropod vector
WNV–> culex species
YFV, DENV, ZIKV–> Aedes species
mosquitos and ticks trasmit
Explain where we see encephalitis and hemorrhagic fever
WNV–> human (mammals) are dead-end hosts
YFV, DENV, ZIKV–> sustained human transmission
resovoir goes from birds, to mosquitos, to human
Humans don’t pass it on very well bc Flavi does not replicate wll in humans
Explain flavivirus replication
- Binding
- Endocytosis
- Uncoating
- Translation (polyprotein)
- RNA replication
- Morphogenesis & Transport: They do not bud from plasma membrane, they bud at the intracellular membrane (GOLGI APPARATUS) into a vesicle and is secreted outside the cell
- Vesicle fusion and virus release
What is wired for flavivirus replication?
what is req for replication?
That when the virus makes the protein, it uses the ER membrane to insert its polyproteinn into the ER. Some portions are going to be in the inside (ER lumen) and some are outside (cytoplasm).
Flavi is using host ribsomes on rough ER to make viral protein, in intertwines itself on membrane of ER (this is during step 7 translation)
Explain flavivirus protein processing
Cytoplasm of flavi requires a different enzyme from the lumen.
* NS3 (+NS2B) is used to cleave certains parts of membrane in the cytoplasm
* Signal peptidase (cellular) is used to cleave certains parts of membrane in ER lumen
proteins are cleaved in a specfific order.
What are the serotypes and vectors of Dengue Virus?
4 serotypes (DEN 1,2,3,4)
all serotypes can cause severe and fatal disease
each serotype provides specific lifetime immunity and short-term cross-immunity (you get immunity for a diff serotype)
Vectors: aedes aegypti and aedes albopictus
dengue is the most impt flavi, it causes the most disease
Explain the extrinsic and intrinsic incubation period of dengue virus by Aedes aegypti
Extrinsic (incubation in mosquito vector): Human is infected with veremia (virus in blood). Gets bitten b y mosquito and infects mosquito with dengue. and virus is replicating in salivary glands for about 12 days.
Intrinsic (incubation in humna host): Same Mosquito bites a different human, virus is in a new host and starts to replicate and there is viremia in human.
What is the global distribution of dengue virus vectors (Aedes aegypti and aedes albopictus)?
Aedes aegypti: likes tropical and subtropical regions EX: South America
Aedes albopictus: more in the US than aegypti, but mostly in Southeast Asia
What are the dengue clinical syndromes?
Dengue fever and severe dengue
What is dengue fever?
high Fever plus:
* aches and pains (eye pain, typically behind the eyes, muscle, joint, or bone pain)
* nausea, vomiting
* rash
* symptoms of dengue typically last 2-7 days
bolded are major sx
What is severe dengue?
Dengue fever followed by:
* Belly pain, tenderness
* vomiting (at least 3 times in 24 hours)
* bledding from the nose or gums
* vomiting blood, or blood in the stool
* feeling tired, restless, or irritable
referred to as Dengue hemorrhagic fever (DHF) or Dengue Shock Syndrome (DSS)
you get signs of severe dengue after dengue fever b/c of ade
Previous infection by different DENV serotype can predispose someone to what?
Severe dengue (antibody dependent enhancement)
Explain Antibody-dependent enhancement (ADE)
- You get inf. with Dengue again and the heterotypic antibody from PREV inf (w/ a diff serotype) binds to virus but CANNOT neutralize
- Antibody is recognized by FC receptor on macrophage/monocytes.
- SO we have binding of the virus to binding of the antibody to the FC receptor which facilitates inf of monocytes
- Monocytes becomes inf and replicates a lot of virus. Leads to severe dengue
when you are infected, you make abs to 1 serotype. When you get infected again with a different serotype abs are not as protective so you are at higher risk of getting severe dengue w/ diff serotype.
How can dengue be prevented?
Vaccines
1. Dengvaxia: live attenuated based on a YF virus vaccine. Targets all 4 serotypes.
2. TAK-003/Qdenga (inactived rDEN2): 4 serotypes into DEN2 virus and it inactivated dengue, similar to flu vaccine
3. In development: TV-003/005 (live attenuated, rDEN4) 4 serotypes in the vaccine
Mosquito control
Explain mosquito control for the prevention of dengue virus.
- Create transgenic mosquito in lab (OXITEC MOSQUITO): You insert a self-limiting gene into the mosquito to where it needs tetracycline to survive. You release mosquito into the wild and they breed, and they die bc no tetracycline.
- WMel Wolbachia (Wolb+): wolb+ is an endosymbiotic bacteria creating in lab that lives in the mosquito and it disprupts ER , disrupting polyprotein from winding along the membrane. It also disrupts golgi apparatus (prevents budding of virus) so no more production of virus.
2nd way doesnt replicate virus w/o killing mosquito
KNOW WOLBACHIA
About _ in _ people infected with ZIka virus become symptomatic.
1 in 5
usually mild (days to week), hospitalization uncommon, low fatality
What are some characteristc clinical findings of zika virus?
acute onset of fever with
1. maculopapular rash
2. arthralgia
3. conjunctivitis
4. myalgia
5. headache
What are come complications of Zika virus?
- Guillan-Barre syndrome
- Microcephaly
* associated with infection in 1st trimester
* virus infects neuro-progenitor cells in ventricular (VZ) and subventricular (SVZ) zones –> cell death
- Zika crosses the placental tissue and infects the fetus in the VZ and SVZ. With these cell death, this prevents development of the brain (these cells make the skull) which leads to microcephaly.
microcephaly is a major sx and is unique to zika
What is the molecular epidemiology of Zika virus?
- Zika virus is taking a whole bunch of mutations in order to become better adapted to humans in oder to transmit like corona
- Its the sequentiual acquisition of specific mutation that allows the virus to go from relatively benign to a virus that cause disease