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Summary Study Unit 2 Viruses Part 2

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Part 2 of the study unit on viruses.

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Subido en
18 de junio de 2020
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28
Escrito en
2019/2020
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GENETICS 344: ADVANCED TOPICS IN GENETICS

STUDY UNIT 2: VIRUSES

LECTURE 5

8. TOPICAL VIRUS EXAMPLES
8.1 EBOLA VIRUS DISEAS (EVD)
• Symptoms usually begin with influenza-like stage
o Fatigue, Fever, Headaches, Joint&muscle&adominal pain
• Incubation period = 2 – 21 dys
• Bleeding phase
o 5 – 7 dys after 1st symptoms
o Internal & subcutaneous bleeding – Reddening of eyes & bloody vomit
• Death within 7 – 16 dys after 1st symptoms
• EVD outbreaks can have case fatality rate of up to 90%
• History:
o Named after Ebola river in Central African Republic
o 1976 – 2013 – WHO: 1 716 cases
o 2014 – 11 300 deaths
• Outbreak in 2018 – started in Congo
o Infected 2 620 people
o Killed 1 762 – mortality = 67%
o Confirmed case in big city with airports, etc – easy spread via transit
o Ebola doesn’t spread very rapidly
• Spread is dependent on:
o Size of particle
o Droplet spread
o Host receptors
o Onset of symptoms
o Stability of virion
• EVD occurs after ebola virus is transmitted to initial human via contact with infected
animal’s body fluids
o Zoonotic disease
• Human-to-human transmission via:
o Direct contact with blood/bodily fluids from infected person
o Contact with contaminated medical equipment
• Potential for widespread EVD infections is considered low
o Disease is only spread by direct contact with secretions from infected person
• Quick onset of symptoms
o Easier to ID sick individuals
o Limits person’s ability to spread disease by traveling
• Airborne transmission hasn’t been documented during EVD outbreaks
• Are infectious as breathable 0.8 – 1.2 μm droplets
• Fruit bats = Natural reservoir of virus – not affected by virus

,8.1 EBOLA VIRUS DISEAS (EVD)
• Etiology:
o EVD is caused by 4 of 5 viruses in genus Ebolavirus / family Filoviridae/ order
Monogevirales:
o 4 disease-causing viruses:
▪ Bundibugyo virus (BDBV)
▪ Sudan virus (SUDV)
▪ Taï Forest virus (TAFV)
▪ Ebola virus (EBOV, ZEBOV, Zaire virus)
o Ebola virus is most dangerous – responsible for largest number of outbreaks
o 5th virus = Reston virus (RESTV)  Not thought to be disease-causing in humans




• Ebola Virus Structure:
o Filamentous particles
o May appear in shape of shepherd’s crook / in shape of U or 6
o May be coiled / branched
o 80 nm in width – ranges from 974 – 1086 nm in length
• Ebola Virions:
o Linear
o Non-segmented
o ss(-)RNA
o Non-infectious
o Possess inverse-complementary 3’ & 5’ end
o Don’t possess 5’-cap
o Are not polyadenylated
o Not covalently linked to protein
o 19 kb long & contain 7 genes
o Carries polymerase with it to start process before replication

, 8.1 EBOLA VIRUS DISEAS (EVD)
• Replication
o Ebola virus binds to cells with anchor protein (GP) on surface of virus
o Attachment to host receptors through GP glycoprotein like DC sign & DC-SIGNR
o Cellular receptor like HAVCR1 (TIM1) binds phosphatidyl serine on virion membrane
▪ Signal is transduced into cell that trigger micropinocytosis program allowing
virion entrance
o Macropinocytosis
▪ Mechanism for cell to ingest extracellular liquid & dissolved molecules
▪ Exploited by viruses to get in cells
o GP1 interacts with host NPC1 in late macropinosome
▪ Promotes fusion of virus membrane with vesicle membrane
o Ribonucleocapsid is then released into cytoplasm
o Sequential transcription
▪ Viral mRNAs are capped & polyadenylated by polymerase stuttering in
cytoplasm
o Replication presumably starts when enough nucleoprotein is present to encapsidate
neo-synthetized antigenomes & genomes
o Ribonucleocapsid interacts with matrix protein
▪ Buds via host ESCRT complexes from plasma membrane
▪ Releasing virion
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