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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

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The Ebola Virus

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  1. The Ebola Virus Mario Rodriguez Solivan 200-90-3863

  2. 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

  3. Taxonomy • Group: Group V • Order: Mononegavirales • Monos = single(strand) • Negare = negative • ssRNA (-) • Family: Filoviridae • Genus: Ebolavirus • Species: Zaire, Reston, IvoryCoast, Sudan, Bundibugyo

  4. Morphology • Pleomorphic • Filamentous • 800-14,000 nm in length • 80-100 nm diameter • 970nm smallest found that can cause infection

  5. 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

  6. 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

  7. Gene Map

  8. 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

  9. Ecological Cycle

  10. 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

  11. DifferentSpecies • 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

  12. Different Species • Côted'Ivoire • AKA Taï Forest and Ivory Coast • First found in Taï Forest of theCôted'Ivoire in Africa • Highlyinfectuous to chimpanzees • Swissethologistinfectedduringnecropsyonthechimps • “Dengue-like” symptoms a weeklater • Transported to Switzerlandfortreatment • 2 weekslatershewasreleasedfrom hospital • Didnotfullyrecoverfor 6 weeksafterrelease

  13. Viral Life Cycle • Virion entrance • Endocytosis • Formation of endosome • Endosome binds with lysosome • Formation of endolysosome • Acidification of endolysosome • Release genetic material • Replication of ssRNA(-) • Form (+) strand • Transcription of newly formed ssRNA(+) • Assisted by VP30, VP35 and L protein • Translation • mRNA encoding for GP • Travel to ER • Where GP is synthesized • GP is further modified in Golgi • Delivered to plasma membrane in secretory vesicles • All viral proteins now assemble with the membrane associated proteins • Virions bud from cell surface • GP is also secreted

  14. Pathogenesis • Hemorrhagic fever • Multisystem syndrome • Damaged vascular system • Internal bleeding • Body regulations abnormal

  15. Mode of Attack • Endothelial cells • Walls of vascular system • Cytokines • Inflammation • Hepatic Cells • Swelling • Cytokines • TNF-alpha, IL-6, IL-8 • Hemorrhages all over

  16. 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

  17. 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!

  18. Prevention NO VACCINES AVAILABLE 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 • 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 countries markets

  19. TIM-1 T-cell immunoglobulin and mucin domain 1 ARD5 Monoclonal Antibody Blocked EBOV binding and infection Anti-TIM-1 New antiviral approach • This human protein binds to the EBOV GP • Recent Study • Reduction of this receptor reduces infection

  20. Statistics

  21. 1976-2012

  22. 2014 • http://www.euronews.com/2014/04/12/west-africa-doctors-fight-to-contain-ebola-outbreak/ • https://www.youtube.com/watch?v=5BRJPCsUM2w

  23. 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

  24. Citations • http://jvi.asm.org/content/77/3/1793 • http://en.wikibooks.org/wiki/Structural_Biochemistry/Glycoproteins/Ebola_Virus • 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 • http://www.microbiologytext.com/index.php?module=Book&func=displayarticle&art_id=494 • http://www.stanford.edu/group/virus/filo/eboci.html • http://www.pnas.org/content/108/20/8426 • http://www.cell.com/cell/abstract/S0092-8674(13)00886-6 • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485981/ • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100998/figure/fig01/ • http://www.cdc.gov/vhf/ebola/outbreaks/guinea/ • http://wwwnc.cdc.gov/travel/notices/alert/ebola-guinea • 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/

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