Marburgviruses and Ebolaviruses History, Fiction, and the Facts

1
Marburgviruses and Ebolaviruses History,
Fiction, and the Facts
MIT Faculty Dinner Series on Biosecurity
September 29, 2005 Jens H. Kuhn
2
The Media and Public Perception
3
The Preston-Outbreak Scenario

• An ebolavirus emerges in Africa and is imported
  into the U.S. by its monkey host or a sick
  patient
• The virus is highly contagious, spreads quickly
  and infects thousands of people en route
• The infections are characterized by crashing
  patients with liquefying organs patients die
  from extensive blood loss
• The military acquires the virus and builds the
  perfect biological weapon

4
Phylogeny, Endemicity, Human and Animal Case
Numbers
5
Filovirus Hosts, Transmission, Clinical
Presentation, and Treatment
6
Pathogenesis
7
Filovirus Particle Characteristics
8
Molecular Biology
VP24
t
L
VP35
NP
l
GP
VP30
VP40
P -5
3-HO
IR
19,104
1
IR
IR
IR
OR
IR
9
Biosafety and Biosecurity Classification
10
Preston and Outbreak Revisited

• True
• Filoviruses are endemic in Africa and could be
  imported

• False
• Primates are filovirus hosts
• Filoviruses are very contagious
• Filoviruses are very stable entities
• Hemorrhages and liquefying organs are typical
  symptoms
• Filoviruses are perfect biological weapons

11
The Media and Professional Perception
12
The Alibek Scenario

• The Soviet KGB acquires marburgviruses covertly
  by recovering corpses of the 1967 marburgvirus
  disease outbreak in Germany
• Military work begins immediately to create
  powerful bioweapons
• A laboratory accident provides extremely virulent
  strains U and V
• At the end of the 1980s, chimeras of these
  strains and variola virus are created

13
Soviet Filovirus Research
14
Some Publications of Concern

• Volchkov V. E., et al. (2001) Recovery of
  Infectious Ebola Virus from Complementary DNA
  RNA Editing of the GP Gene and Viral
  Cytotoxicity. Science 291 1965-1969
• Towner J. S., et al. (2005) Generation of eGFP
  expressing recombinant Zaire ebolavirus for
  analysis of early pathogenesis events and
  high-throughput antiviral drug screening.
  Virology 332 20-27
• Vorontsova L. A. (1992) Electron microscopic
  studies of Marburg virus and pathological changes
  in animal organs caused by this virus.
  Dissertation to obtain the degree Candidate of
  Biological Science. SCRVB "Vector" Russia
• Zelenkov V. N., et al. (1990) Cultivating Marburg
  virus on Vero cell monolayers treated with
  1-chloromethylsilatran and 1-etoxysilatran. In
  Biological activity of compounds containing
  silicon, germanium, and tin. Abstract collection
  of the 4th All-Union conference, June 12 - 14,
  U.S.S.R. Academy of Sciences, Irkutsk Institute
  of Organic Chemistry, U.S.S.R., pp 6
• Frolov V. G. (1994) Study of the factors
  determining stability and dynamics of
  thermoinactivation of Marburg virus in
  freeze-dried media. Development of an
  "accelerated storage" test for prediction of
  Marburg virus activity during long-term storage.
  Dissertation to obtain the degree Candidate of
  Technological Science. SRCVB "Vector, Russia

15
Alibek Revisited

• True
• Soviet laboratory infection provided opportunity
  to characterize new filovirus strain

• False
• KGB acquired filoviruses
• All filovirus research was classified
• Strains U and V were basis of developed Soviet
  bioweapons?
• Filovirus chimeras were created at the end of the
  1980s

16
Summary

• Overall human filovirus infection case numbers
  and their properties should make these viruses a
  low research priority (HIV-1, TB!)
• Filoviruses are interesting bioweapon candidates
  for state-sponsored programs because of new
  possibilities for manipulation developed in the
  West in recent years
• However, manipulation of filoviruses demands
  highly skilled researchers. The development of an
  efficient filovirus bioweapon still requires
  overcoming major obstacles such as instability
  and ineffective transmission