The Ebola VirusMario Rodriguez Solivan200-90-3863

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 foundthat 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

Up to 90% mortality rate Sudan

Region of Sudan and Uganda High 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 Cycle1. Virion entrance

Endocytosis

2. Formation of endosome3. Endosome binds with lysosome

Formation of endolysosome

4. Acidification of endolysosome Release genetic material

5. Replication of ssRNA(-) Form (+) strand

6. Transcription of newly formed ssRNA(+)

Assisted by VP30, VP35 and L protein

7. Translation mRNA encoding for GP

8. Travel to ER Where GP is synthesized

9. GP is further modified in Golgi Delivered to plasma membrane

in secretory vesicles

10. All viral proteins now assemble with the membrane associated proteins

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 Monoclonal antibodies

that bind to NP Determine the species

Reverse transcription-PCR Primers designed

specifically for NP region Real-time quantitative RT-

PCR Green Dye Primer set used to

amplify the L-protein genes

Antigen-capture ELISA 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!

PreventionNO VACCINES AVAILABLE

Avoid traveling to areas of known outbreaks Check CDC before

traveling Wash your hands

frequently Like any other infectious

disease Avoid bush meat

Wild animal meat in developing countriesmarkets

Avoid contact with infected people Body fluids, exposed

tissues, blood, semen Follow infection-control

procedures 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.euronews.com/2014/04/12/west-africa-doctors-fight-to-contain-ebola-outbreak/

https://www.youtube.com/watch?v=5BRJPCsUM2w

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

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http://edusanjalbiochemist.blogspot.com/2014/04/the-deadly-ebola-virus-frequently-asked.html

http://www.iflscience.com/health-and-medicine/new-antiviral-shows-potential-against-ebola

http://www.elmundo.es/salud/2014/04/16/534d2762ca47414d4e8b456d.html?cid=SMBOSO25301&s_kw=twitter

http://www.virology.ws/2012/01/18/how-lethal-is-ebolavirus/

https://www.google.com.pr/search?q=province+orientale+&oq=province+orientale+&aqs=chrome..69i57j0l5.5777j0j7&sourceid=chrome&essm=93&ie=UTF-8

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http://www.who.int/csr/don/2014_04_ebola/en/

http://wwwnc.cdc.gov/eid/article/3/1/97-0107_article.htm

http://www.microbiologytext.com/index.php?module=Book&func=displayarticle&art_id=494

http://www.ncbi.nlm.nih.gov/pubmed/24283270

http://www.infectioncontroltoday.com/news/2014/05/ebola-virus-disease-in-west-africa-226-cases-149-deaths.aspx

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459631/

http://www.euronews.com/2014/04/12/west-africa-doctors-fight-to-contain-ebola-outbreak/