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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
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Biosafety Level 4 Lab
Designed specifically to create genetically altered viruses
Bioweaponization-
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U.S. was considered “deep target”
–
potentially aerosolized
• 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.
2.
3.
4.
Zaire
Sudan
Reston
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 Deltapeptide.
• 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
great apes  humans
• May infect humans
directly
– Dry season
• More contact because of
food competition
• Bats’ immune systems
modified
• Virus reproduces easier
• In 2001-03
– Survey of 1,030 animals
(including 679 bats) from
Ebola-affected areas
– Found three bat species
– Viral genome fragments
(RNA) in the liver and spleen
– Evidence of immune
response
• antibodies against virus in
the serum
Transmission of Ebola Virus
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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
• Fever (at least 102°F)
• Weakness & exhaustion
• Pain
– Severe headache
– Muscles & joints
– Abdominal pain
• Sore throat
• Nausea
• Dizziness
Progressed Symptoms
• Vomiting
• Diarrhea
• Extensive bleeding
– Red eyes
• hemorrhage of sclerotic
arterioles
– From mouth, nose, eyes,
rectum & mucouse
membranes
• Maculopapular rash
– Spreads over the body (often
hemorrhagic)
• Other secondary symptoms
– Hypotension , Hypovolemia ,
Tachycardia
– Organ damage
– Internal and external bleeding
Tissue Damage leads to
Hemorrhaging
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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
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Infection Prevention
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Isolation
communication
Limit direct contact
Monitor those who had lose contact
with infected
Disinfect reusable equipment
Sterilize equipment
Lab Safety Precautions
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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
a cure for Ebola
- Decreased Fear
- A cut of the profits
biowarfare threat list;
however, 4 other weapons
labs exist with no U.S.
inspection
- 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
– CDC classifies it as:
• Category A bioterrorism
agent
– Sudden, severe onset of
symptoms
– Believed to hide out in
animals
– No approved vaccine or
treatment
– Short incubation period
Smallpox Virus
– CDC classifies as
• Category A bioterrorism agent
– Incubation period between
contraction and the first obvious
symptoms of the disease is usu. 12-14
days
– Initially vague, flu-like symptoms, turn
into severe symptoms (fever, severe
pain, characteristic rash)
– Humans are the only natural host
– Historic death rate of 1 in 3
– Vaccination in 1967
• May kill victim before
• Effective if administered up to 4 days
transmitted to others (high
after viral exposure and before rash
appearance
death rate)
• 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
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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
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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!