Transcript The Ebola Virus

The Ebola
Virus
Mario Rodriguez Solivan
200-90-3863
What is Ebola?
 First
discovered in 1976
 Severe often fatal viral
disease

Human and non-human
primates
 Lytic
life cycle
 Does
not integrate in
host genome
 Causes
viral
hemorrhagic fever


With an incubation
period of 2 to 21 days
Internal bleeding
Taxonomy

Group: Group V

Order: Mononegavirales
Monos = single(strand)
 Negare = negative



ssRNA (-)
Family: Filoviridae

Genus: Ebolavirus

Species: Zaire, Reston, Ivory Coast, Sudan,
Bundibugyo
Morphology
 Pleomorphic
Filamentous
 800-14,000 nm in length
 80-100 nm diameter
 970nm smallest found
that can cause infection

Genes
7
main segments app. 19kb

NP: structural nucleoprotein
N
terminal interacts with the RNA to contact the rest of
the proteins in matrix and envelope

VP35: plays a strong roll in mRNA synthesis and
replication of the negative strands

VP40: MAIN TARGET for research as of 2012
 Bridges
the lipid envelope with the nucleocapsid
 Mutations or removal of the protein have shown to
attenuate the virus
Genes

GP/SGP: glycoprotein and secreted glycoprotein
 Non-structural
can confound the immune system

VP30: important for budding out of membrane

VP24: Inhibits INF-alpha/beta and INF-gamma
signaling

L: L-RNA polymerase

Copies the negative strand to make the positive
transcripts
Gene Map
Origin
 New

serological studies
Fruit bats (Pteropodidae)
 Contain
specific antibodies to Ebola
 Probable Natural reservoir

Chimpanzee, Gorillas, smaller primates
 Carriers

of the virus
Some strains and species will affect them
Ecological Cycle
Different Species

Zaire


Congo region of Africa (Zaire)
Most lethal of all species


Sudan


Region of Sudan and Uganda
High mortality rate


Up to 90% mortality rate
App. 53%
Bundibugyo


Bundibugyo District of Uganda
Province Orientale Democratic Republic of Congo

2007 – 2012 App. 36.3% moratality rate
Different Species
 Reston

Named after Reston, Virginia
 First

Discovered in crab-eating macaques
Mutation from other Ebola Virus
 Mostly

non-pathogenic towards humans
Philippines caused human infection

Less aggressive than African Ebola
 Extremely
hazardous to monkeys
Different Species
 Côte



d'Ivoire
AKA Taï Forest and Ivory Coast
First found in Taï Forest of the Côte d'Ivoire in Africa
Highly infectuous to chimpanzees
 Swiss ethologist infected during necropsy on the
chimps


“Dengue-like” symptoms a week later
Transported to Switzerland for treatment


2 weeks later she was released from hospital
Did not fully recover for 6 weeks after release
Viral Life Cycle
Virion entrance
1.

Endocytosis
Formation of endosome
Endosome binds with lysosome
2.
3.

Formation of endolysosome
Acidification of endolysosome
4.

Release genetic material
Replication of ssRNA(-)
5.

Form (+) strand
Transcription of newly formed
ssRNA(+)
6.

Assisted by VP30, VP35 and L
protein
Translation
7.

mRNA encoding for GP
Travel to ER
8.

Where GP is synthesized
GP is further modified in Golgi
9.

Delivered to plasma
membrane in secretory
vesicles
All viral proteins now assemble
with the membrane associated
proteins
10.


Virions bud from cell surface
GP is also secreted
Pathogenesis
 Hemorrhagic

fever
Multisystem syndrome
 Damaged
vascular system
 Internal bleeding
 Body regulations abnormal
Mode of Attack
 Endothelial


cells
Walls of vascular system
Cytokines
 Inflammation
 Hepatic

Cells
Swelling
 Cytokines

TNF-alpha, IL-6, IL-8
 Hemorrhages
all over
Symptoms
 First







signs
Headache
Fever
Joint and muscle
aches
Weakness
Vomiting
Diarrhea
Fatigue
 Advanced




signs
Internal bleeding
Orificial bleeding
Cutaneous
ruptures
Hepatic
inflamation
 Cytokines

Renal disfunction
Diagnostics

Virus isolation



Reverse transcriptionPCR


Monoclonal antibodies
that bind to NP
Determine the species

Antigen-capture ELISA




Primers designed
specifically for NP region
Real-time quantitative
RT-PCR


Green Dye
Primer set used to
amplify the L-protein
genes


Monoclonal antibodies
NP, VP40, GP
Immunizing mice with
rNP
React with epitopes in
carboxyl groups at NP
terminals
AWESOME FACT!
The rNP of the Reston
EBOV could only detect
Reston NP… but the
Zaire rNP could detect
NP from all 5 species!
Prevention
NO VACCINES AVAILABLE

Avoid traveling to
areas of known
outbreaks


Wash your hands
frequently


Check CDC before
traveling
Wild animal meat in
developing countries
markets
Avoid contact with
infected people



Body fluids, exposed
tissues, blood, semen
Follow infection-control
procedures

Like any other infectious
disease
Avoid bush meat


Gloves, masks, eye
shields, careful
disinfections
Don't handle remains

Dead bodies are still
contagious
TIM-1
T-cell immunoglobulin
and mucin domain 1
 This
human protein
binds to the EBOV
GP

Recent Study

Reduction of this
receptor reduces
infection
ARD5
 Monoclonal
Antibody

Blocked EBOV
binding and
infection
 Anti-TIM-1

New antiviral
approach
Statistics
1976-2012
2014

http://www.euronew
s.com/2014/04/12/w
est-africa-doctorsfight-to-containebola-outbreak/

https://www.youtube
.com/watch?v=5BRJ
PCsUM2w
Questions

What kind of genetic material
does Ebola have?
 A. dsRNA+
 B. ssDNA C. ssRNA D. dsDNA E. ssRNA+

What GROUP does EBOV belong
to?
 A. V
 B. III
 C. I
 D. II
 E. IV

In what organelle is GP
(glycoprotein) synthesized?
 A. Mitochondria
 B. Nucleus
 C. Golgi
 D. ER
 E. Lysosome

Why is it suspected that the
fruit bat is the natural
reservoir for EBOV?...
 ANSWER OUT LOUD
Citations

http://jvi.asm.org/content/77/3/1793

http://www.cell.com/cell/abstract/S0092-8674(13)00886-6

http://en.wikibooks.org/wiki/Structural_Biochemistry/Glyco
proteins/Ebola_Virus

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485981/
http://edusanjalbiochemist.blogspot.com/2014/04/thedeadly-ebola-virus-frequently-asked.html


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100998/fi
gure/fig01/
http://www.iflscience.com/health-and-medicine/newantiviral-shows-potential-against-ebola

http://www.cdc.gov/vhf/ebola/outbreaks/guinea/


http://wwwnc.cdc.gov/travel/notices/alert/ebola-guinea

http://www.elmundo.es/salud/2014/04/16/534d2762ca474
14d4e8b456d.html?cid=SMBOSO25301&s_kw=twitter

http://www.who.int/csr/don/2014_04_ebola/en/

http://www.virology.ws/2012/01/18/how-lethal-isebolavirus/

http://wwwnc.cdc.gov/eid/article/3/1/97-0107_article.htm


https://www.google.com.pr/search?q=province+orientale
+&oq=province+orientale+&aqs=chrome..69i57j0l5.5777j0j7
&sourceid=chrome&essm=93&ie=UTF-8
http://www.microbiologytext.com/index.php?module=Bo
ok&func=displayarticle&art_id=494

http://www.ncbi.nlm.nih.gov/pubmed/24283270

http://www.microbiologytext.com/index.php?module=Bo
ok&func=displayarticle&art_id=494

http://www.infectioncontroltoday.com/news/2014/05/ebo
la-virus-disease-in-west-africa-226-cases-149-deaths.aspx

http://www.stanford.edu/group/virus/filo/eboci.html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459631/

http://www.pnas.org/content/108/20/8426

http://www.euronews.com/2014/04/12/west-africadoctors-fight-to-contain-ebola-outbreak/