Exam3Lec3Arbobiruses/EmergingViralInfections Flashcards

1
Q

Explain the emergence of urban transmission of flaviviruses

A
  1. 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.
  2. 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
  3. Spillback into enzootic cycle: Humans travels back to ecosystem with a modified virus and brings it back inot the ecosystem.
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2
Q

Basic info about flavi viruses

A

rna (+) ss, icosahedral, cytoplasmic replication

flavi virusews are arboviruses meaning that they are arthropod-borne viruses, We get bitten by mosquitos or ticks

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3
Q

What are 5 arboviruses we see in FL?

A
  1. Dengue
  2. West nile
  3. Zika
  4. Chikungunya
  5. EEE
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4
Q

Did we have any human cases this year for Chikungunya in FL?

A

NO

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5
Q

For Dengue virus cases, how may importations and locally acquired in FL?

A

639 importation and 36 locally acquored. 92% importations from cuba (~60% DEN3 serotype)

cases go up every yr and they come from Cuba

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6
Q

What is the vector of flavivirus?

A

Arthropod vector
WNV–> culex species
YFV, DENV, ZIKV–> Aedes species

mosquitos and ticks trasmit

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7
Q

Explain where we see encephalitis and hemorrhagic fever

A

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

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8
Q

Explain flavivirus replication

A
  1. Binding
  2. Endocytosis
  3. Uncoating
  4. Translation (polyprotein)
  5. RNA replication
  6. 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
  7. Vesicle fusion and virus release
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9
Q

What is wired for flavivirus replication?

what is req for replication?

A

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)

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10
Q

Explain flavivirus protein processing

A

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.

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11
Q

What are the serotypes and vectors of Dengue Virus?

A

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

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12
Q

Explain the extrinsic and intrinsic incubation period of dengue virus by Aedes aegypti

A

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.

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13
Q

What is the global distribution of dengue virus vectors (Aedes aegypti and aedes albopictus)?

A

Aedes aegypti: likes tropical and subtropical regions EX: South America
Aedes albopictus: more in the US than aegypti, but mostly in Southeast Asia

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14
Q

What are the dengue clinical syndromes?

A

Dengue fever and severe dengue

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15
Q

What is dengue fever?

A

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

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16
Q

What is severe dengue?

A

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

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17
Q

Previous infection by different DENV serotype can predispose someone to what?

A

Severe dengue (antibody dependent enhancement)

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18
Q

Explain Antibody-dependent enhancement (ADE)

A
  1. You get inf. with Dengue again and the heterotypic antibody from PREV inf (w/ a diff serotype) binds to virus but CANNOT neutralize
  2. Antibody is recognized by FC receptor on macrophage/monocytes.
  3. SO we have binding of the virus to binding of the antibody to the FC receptor which facilitates inf of monocytes
  4. 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.

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19
Q

How can dengue be prevented?

A

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

20
Q

Explain mosquito control for the prevention of dengue virus.

A
  • 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

21
Q

About _ in _ people infected with ZIka virus become symptomatic.

A

1 in 5

usually mild (days to week), hospitalization uncommon, low fatality

22
Q

What are some characteristc clinical findings of zika virus?

A

acute onset of fever with
1. maculopapular rash
2. arthralgia
3. conjunctivitis
4. myalgia
5. headache

23
Q

What are come complications of Zika virus?

A
  1. Guillan-Barre syndrome
  2. 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

24
Q

What is the molecular epidemiology of Zika virus?

A
  • 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
25
What are some clinical differences between chikungunya, dengue, and zika?
We mostly see fever (>39 degrees), arthralgia, and arthritis with chikungunya. we mostly see conjunctivitis with Zika. We mostly see hemorrhage with dengue We mostly see shocl with Dengue ## Footnote molecular tets can tell us exactly what we have b/c sx are similar for these
26
Basc info about coronavirus
RNA (+) ss 30kb enveloped helical cytoplasmic replication ## Footnote largest genome
27
Coronaviruses mostly cause what type of illness?
Respiratory and GI
28
True or False, Coronavirus is the 2nd leading cause of "common cold"
True ## Footnote rhinovirus is number one
29
What are novel coronaviruses?
1. SARS-1 2. MERS 3. SARS-2 ## Footnote more types of coronaviruses are coming out
30
Explain the emergence of SARS-like coronaviruses | how/when coronavirus came about
* Severe Acute Respiratory Syndrome (SARS CoV-1) - was seen 2002-2003 in South china, bat origin, and didn't spread much * Middle East Respiratory Syndrome (MERS CoV) - 2012-present, Comes out frequently but doesnt have a lot of cases, mostly located in Saudi Arabia
31
What is the structure of Sars Cov-2
Structural * Spike (S) protein: We immunize against this protein and it's responsible for receptor binding * Envelope (E) protein: responsible for entry * Membrane (M) protein: responsible for making virus itself * Nucleocapsid (N) protein and viral RNA: * Nonstructural proteins: Polymerase, protease, etc 2/3 of genome is made of replication (non-structual protein) * Accessory Proteins
32
What is the relation between emerging coronaviruses and bats?
Bats are among the most ancient mammals Bats represent 20% of mammalian diversity (over 1,400 species) Bats have wide geographical range and can infect human directly or through intermediate hosts (They are everywhere) ## Footnote it was found that the genome of coronavioruses is closely related to bat virus, specifically sars cov-1
33
Explain the hypothesis for viral persistance in bats
* There are differences in innate immunity (IFN, etc)and adaptive immunity. They are carries of virus w/o sx * Flight of bats results in increased body temperature, ROS
34
How is SARS Cov-2 transmitted?
person-to-person spread (symptomatic/asymptomatic) main route is airbone **respiratory droplets** **direct**: respiratory droplets produces through cough, sneeze, speech, breathing **indirect**: fomites on surfaces(half-life varies by surface and temperature~ abt 24h) live virus and viral RNA have been detected in stool samples ## Footnote note that small droplets can travel very far and quickly large droplets fall
35
Explain the SARS CoV-2 clinical course
Flu-like symptoms between 2-11 days after exposure (average = ~ 5 days) * common: fever, dry, cough, fatigue, SOB * other: myalgia/arthralgia, headachr, sore throat, chills, chest pain, new confusion, new loss of **smell/taste (anosmia/ageusia)**, hypoxemia * **rare**: nausea w/ or w/o vomiting, abdominal discomfort with some diarrhea, exanthems (COVID toes etc), coagulopathy ## Footnote coagulopathy is a defect in clotting, its a bigger problem now
36
What are the complications and post-acute sequelae of SARS-CoV-2?
The SARS-CoV-2 virus gains entry into the cells of multiple organs via the ACE2 receptor which can cause: * Severe COVID-19 1. pneumonia 2. severe inflammation in lungs 3. hypercoagulability (HUGE probelm, pts are put on blood thinners)-mentioned this twice **post acute sequelae from SARS CoV-2 (PASC or "long COVID")** not one set of sx, but many sx. So a large # of diff inf, in different organ systems that can lead to spectrum of sx that we see in long covid ## Footnote 81% of sx are mild/moderate, 14% hospitalization, 5% critical
37
How can you diagnose corona?
Samples: nasopharyngeal (mid-turbinate, nasal) swab and Saliva Tests: nucleic acid * lab based PCR (QUANTITATIVE) ELISA * Point-of-care (QUALITATIVE) antigen * lateral flow (QUALITATIVE) * Card (QUALITATIVE) ## Footnote quantitative detects amt of mRNA (virus) in sample qualitative tell you yes or no, if you have the virus
38
Explain phylogentetic analysis of SARS CoV-2
Beta version splits off the diff types of coronavirus, which goes dowsn different evolutionary pathways (delta 21I, delta 21J, etc) Moslty radiation of variants come from OMICRON so omicron is the major player variants of corona.
39
Explain prevention and therapy for corona
Vaccines used for prevention (before infection) antivirals/immune stmulation used in early infection Anti-inflamamtory used in pulmonary and systemic phases of host inflammatory phase
40
What are 4 examples for vaccines for corona? specify their platform as well
1. BioNTech/Fosum/Pfizer: LNP-mRNA 2. Moderna/NIAID: LNP-mRNA 3. JNJ/Janssen: Non-replicating viral vector 4. Novavax: protein subunit ## Footnote Also note that Sinovac and BIBP/Sinopharm are both inactivated
41
What are some monoclonal antibodies used as antivirals for corona? | Sars CoV-2 antivirals
* CAS/IMD (Regeneron) EUA * BAM/ETE (Lilly) EUA * SOT (Vir/GSK) EUA * Evusheld (AZ) EUA * BEB (Lilly) EUA note: we cant use them b/c no longer effective against omicron variant, we see monoclonal antibody resistance
42
What is the variants of concern for coronavirus?
More antibody resistance. We see convergent evolution of SARS CoV-2 S, meaning that a lot of these caraitns are out there trying to find a wau around our IS. A lot of these viruses have same combinations of mutations in spike protein to avoid our IS, making them resistant.
43
What are some small molecules used as antivirals for corona?
-A: **RNA dependent RNA polymerase:** **Remdesivir (Gilead)**-FDA approved for hospitalizated(this blocks RNA dependent RNA polymerase) B: **Protease:** * **Paxlovid (Pfizer) EUA:** contrindication due to tritonavir (ppl taking medications like statins)
44
What does NOT work as a therapeutic for severe cases of corona?
* Aspirin * azithromycin * colchicine * hydroxychloroquine * lopinavir-ritonavir * convalescent plasma
45
What does work as therapeutics for severe cases of corona?
* REGN-COV2 * Dexamethasone (Glucocorticoid)-ppl on O2 * Tocilizumab (Anti-IL6R Mab)-blocks IL6 receptor * Baricitinib (JAK inhibitor)-blocks signaling from IL6 receptor * Anankinra (IL-1Ra) ## Footnote These are used for people who are on O2 and ventilaton If you DONT take O2, you dont take any of these