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. VP40 RNA VP30 NP VP24 ? GP1,2 Membrane L VP35 Molecular Biology VP24 L t VP35 l NP VP30 VP40 GP P -5‘ 3‘-HO IR 19,104 1 IR IR IR OR IR

9. Biosafety and Biosecurity Classification

10. 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 Preston and “Outbreak“ Revisited

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. 2 1 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. 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 Alibek Revisited

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