Ebola Virus Microbiology 401 Fall 2007 By: Shahrzad Morim Monica Delgado Janine Gilkes Case Study- Ebola Virus • VECTOR- the State Research Center for Virology and Biotechnology branch • Biosafety Level 4 Lab • Designed specifically to create genetically altered viruses • Bioweaponization- – potentially aerosolized • U.S. was considered “deep target” • The former Soviet Union • Program: – active state-supported bio-weapon research/production (1970’s to mid 90’s) – worked with incurable pathogens While working to develop a vaccine against Ebola virus, one of the scientists accidentally stuck herself with a needle contaminated with virus. She contracted Ebola hemorrhagic fever and died. Ebola Virus Brief Background Family Filoviridae Genus Ebolavirus History First emerged in 1976 Ebola River Valley, Africa Sub-types (well-known) 1. Zaire 2. Sudan 3. Reston 4. Tai (Ivory Coast) Classification Enveloped SS negative-sense RNA Structure Long, filamentous, “thread-like” structure of a filovirus “U” or “6” appearance Ebola Virus • Structure-function analysis of the soluble glycoprotein, sGP, of Ebola virus – Transmembrane protein, GP(1,2) – GP gene encodes the soluble glycoproteins sGP and Delta- peptide. • Genome has 7 genes: – NP, VP35, VP40, GP, VP30, VP24, and L • GP1 Viral Entry • GP2 Fusion and Entry • Likely pH dependent Currently Believed Animal Reservoir of Ebola Virus? • Despite extensive studies, the natural and animal reservoir is unknown – Seems to be the rain forests on the African continent and in the Western Pacific. • Non-human primates as a source of infection for humans – Carcasses of gorillas, chimpanzees and duikers during outbreaks in 2001 and 2003 – High mortality from infection in these species disqualifies them from acting as reservoirs • Other considered Reservoirs – Plants, arthropods, and birds • IRD researchers have identified bats as a potential natural reservoir of Ebola virus – Of 24 plant species and 19 vertebrate species experimentally immunized with Ebola virus, only bats became infected. • No clinical signs were observed in these bats • This is characteristic of a reservoir species Currently Believed Animal Reservoir of Ebola Virus? • Current proposal – Bats • Good vectors – If bats are among the culprits • Likely to pass virus to • In 2001-03 great apes humans – Survey of 1,030 animals • May infect humans (including 679 bats) from directly Ebola-affected areas – Dry season – Found three bat species • More contact because of – Viral genome fragments food competition (RNA) in the liver and spleen • Bats’ immune systems – Evidence of immune modified response • antibodies against virus in • Virus reproduces easier the serum Transmission of Ebola Virus • Direct contact – Blood , secretions , organs • Unsterilized needles • Burial ceremonies • Documented human infections – Handling of infected chimpanzees, gorillas, forest antelopes • Airborne transmission – limited evidence of human-human • Incubation period – 2 to 21 days • Contagiousness – Not during early stages – As the illness progresses, bodily fluids represent an extreme biohazard Symptoms of Ebola Virus Initial Signs Progressed Symptoms • Vomiting • Fever (at least 102°F) • Diarrhea • Weakness & exhaustion • Extensive bleeding • Pain – Red eyes – Severe headache • hemorrhage of sclerotic arterioles – Muscles & joints – From mouth, nose, eyes, – Abdominal pain rectum & mucouse • Sore throat membranes • Maculopapular rash • Nausea – Spreads over the body (often • Dizziness hemorrhagic) • Other secondary symptoms – Hypotension , Hypovolemia , Tachycardia – Organ damage – Internal and external bleeding Tissue Damage leads to Hemorrhaging • Hemorrhagic fever syndrome • late symptoms: – toxic shock, hemorrhaging • Direct tissue damage • liver, combined with massive viremia • Disseminated intravascular coagulopathy • Endothelial susceptibility • Subverts innate and adaptive immune responses • Terminal stages – diffuse bleeding, and hypotensive shock accounts for many Ebola virus fatalities Diagnostic • Specialized laboratory test on blood specimens for detection of – Antigens – Genes of the virus – Antibodies against the virus • New techniques – Non-invasive methods: saliva and urine samples • Diagnosing • ELISA Assay • IgM ELISA • PCR Courtesy of: http://www.ncbi.nlm.nih.gov Infection Prevention and Lab Safety Precautions • Infection Prevention – Isolation – communication – Limit direct contact – Monitor those who had lose contact with infected – Disinfect reusable equipment – Sterilize equipment • Lab Safety Precautions – Education about organism – Sterile environments – Protective clothing – Proper disposal of waste products – Limit contact with contaminated medical equipment – Communication Current Research On Vaccines • One study found that guinea pigs were protected from Ebola virus infection by immunization with plasmids containing the viral genes for either the secreted or transmembrane forms of the viral glycoprotein (GP). This protection was correlated with antibody titer and antigen-specific T-cell responses to secreted GP or membrane GP. • Another study found that harmless-Ebola-like particles (eVLPs) could confer immunological protection from Ebola virus infection. These eVLPs were found to be immunogenic both in vitro and in vivo. Mice were vaccinated with these eVLPs, and developed high titers of Ebola virus specific antibodies, including neutralizing antibodies. Additionally, all the mice in the study were protected from Ebola virus inoculation. Bio-Warfare • Biological warfare (BW) aka biological weapons, is the use of any pathogen, bacteria or virus as a weapon of war. • After initial release of virus, secondary infections may occur as a result of infected individuals traveling from areas of contamination to other locations. • In 1972 the Biological Weapons Convention outlawed creation and storage, but not usage, of these weapons. Benefits and Hazards of U.S Aid • Benefits of US Aid • Hazards of US Aid - Russian Allies - VECTOR removed from - Collaborative efforts in finding biowarfare threat list; a cure for Ebola however, 4 other weapons - Decreased Fear labs exist with no U.S. inspection - A cut of the profits - Difficult to verify whether former Soviet Scientists are using the American supported research for peaceful purposes - Lack of Accountability Which is more dangerous As a Potential Bio-Weapon? Ebola Virus Smallpox Virus – CDC classifies it as: – CDC classifies as • Category A bioterrorism • Category A bioterrorism agent agent – Incubation period between contraction and the first obvious – Sudden, severe onset of symptoms of the disease is usu. 12-14 symptoms days – Believed to hide out in – Initially vague, flu-like symptoms, turn animals into severe symptoms (fever, severe pain, characteristic rash) – No approved vaccine or – Humans are the only natural host treatment – Historic death rate of 1 in 3 – Short incubation period – Vaccination in 1967 • May kill victim before • Effective if administered up to 4 days transmitted to others (high after viral exposure and before rash death rate) appearance • Outbreaks seem to burn out – No effective treatment quickly – In 1979, WHO declared eradication Smallpox (Variola Virus) • Genus: orthopoxvirus • DS DNA: one of the largest viral genomes • Relatively stable – If aerosolized, infective for at least several hours (without sunlight or UV exposure) • Acute contagious disease – Two main forms • Variola major (30% fatal) • Variola minor (<1% fatal) – Two rare forms (almost always fatal) • Hemorrhagic • Malignant Which is more dangerous As a Potential Bio-Weapon? • CDC: an agent must have the following properties to be used for a maximum credible event – Be highly lethal – Be easily produced in large quantities – Be communicable from person to person – Have no treatment or vaccine • Smallpox – Extremely contagious • Transmission through air – Can be produced in large scale – Can spread in any climate or season – Contaminates in a short time – Preventive measures/treatments • Routine smallpox vaccination was discontinued in the U.S. in 1972 • Limited vaccine with questionable potency • Vaccine complications References 1) Adamcek, K., Eanes, M., Shaw, S., Virology Project: Ebola Virus. Retrieved: 11/8/07 • http://www.biosci.ohiou.edu/virology/Ebola 2) Miller, J. Russian Scientist Dies in Ebola Accident at Former Weapons Lab. The New York Times. Published: 5/25/2004. Retrieved: 11/12/2007 • http://query.nytimes.com 3) Pappalardo, J. From Russia, with bugs [US subsidizing Russian Biological Warfare Lab]. Dallas Observer. Published: 6/22/2000. Retrieved: 11/14/07 • http://freepublic.com 4) “Biological Warfare.” Wikipedia: The Free Encyclopedia. Retrieved: 11/12/07 • www.wikipedia.org 5) Emerging Infectious Diseases. National Center for Infectious Diseases. Vol. 5, No.4, July-Aug 1999. Retrieved 11/8/07 • http://www.cdc.gov/ncidod/eid/vol5no4/pdf/v5n4.pdf 6) Tanna, J.H, Preventing “Dark Winter”-The Public Health System’s Role in Strengthening National Security. Vol. 1, No.4, Spring 2002. Retrieved 11/8/07 http://www.carnegie.org/reporter/04/preventing/index.html 7) Leroy, E., Fruit Bats a Reservoir for Ebola Virus. Indigo Base, IRD. November 2005. Retrieved 11/8/07 www.ird.fr/us/actualities/fiches/2005/fiche231.htm 8) World Health Organization. Ebola Haemorrhagic Fever. Retrieved 11/8/07 Refrences • http://www.who.int/mediacentre/factsheets/fs103/en/ 9) Hoenen et al. Ebola Virus: Unravelling Pathogenesis to Combat a Deadly Disease. Trends Mol. Med. May 2006, 12(5): 206-215 10) Leroy, EM, Kimulugui, B, Pourrut, X et al. Fruit Bats as Reservoirs of Ebola Virus. Nature. 2005. 438:575–576 11) Pourrut, X, Kumulungui, B, Wittmann, T et al. The Natural History of Ebola Virus in Africa. Microbes and Infection. 2005. 7:1005–1014 12) Retrieved 11/11/07 • http://www.nytimes.com/packages/html/health/20030506_Ebola_COMPARE/sci_Ebola_COMPARE_01.html# 13) World Health Organization. Smallpox. Retrieved 11/8/07 • http://www.who.int/mediacentre/factsheets/smallpox/en/ 14) September 2003, p. 9733-9737, Vol. 77, No. 18 0022-538 15) BMC Microbiology 2003 3:6 doi:10.1186/1471-2180-3-6 16) www.biomedcentral.com/1471-2180/3/6/figure/F3 www.biosci.ohiou.edu/virology/Ebola/Dectec3.jpg (Courtesy of http://www.ncbi.nlm.nih.gov/ICTVdb/Images/Murphy/ebola_cell.htm 17) World Health Organization • http://www.who.int/mediacentre/factsheets/fs103/en/ • Provisional Revision: 2007 18) Leroy, Eric M., et al. Multibple Ebola Virus Transmission Events and Rapid Decline of Central African Wildlife. Science 303: 387 -389. 2004 19) Facts sheet: Community Health Administration • http://edcp.org/factsheets/ebola.html Journal of Virology Thank you!
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