Laboratory of Infectious Diseases

Alexander G. Pletnev, Ph.D., D.Sci.

Chief, Neurotropic Flaviviruses Section

Dr. Pletnev earned his Ph.D. in 1983 in chemistry from the Russian Academy of Sciences, studying RNA polymerases. Following postdoctoral research at the Novosibirsk Institute of Bioorganic Chemistry, he served as chief of the laboratory of radiochemistry and the laboratory of molecular virology from 1984 to 1993 and became a professor in molecular biology in 1993. In 1990, he received his doctorate of sciences degree in biochemistry and molecular biology from the Russian Academy of Sciences. He joined the Laboratory of Infectious Diseases in 1993 as a visiting scientist and became a senior investigator in 2005.

Description of Research Program

Flaviviruses, such as mosquito-borne West Nile, St. Louis encephalitis, and Japanese encephalitis viruses and tickborne encephalitis viruses, are important neurotropic human pathogens, causing a devastating and often fatal neuroinfection. During the past two decades, both mosquito- and tickborne flaviviruses have emerged in new geographic areas of the world where they were not previously endemic and have caused outbreaks of diseases in humans and domestic animals. Despite many attempts, licensed, safe, and effective live virus vaccines against these neurotropic viruses are not available.

The main goal and objective of our research projects is the development of safe live, attenuated virus vaccines that will be effective in preventing diseases caused by the highly virulent neurotropic viruses of the Flaviviridae family: tickborne encephalitis virus, West Nile virus, and St. Louis encephalitis virus.

Major Areas of Research

• Study of pathogenesis of flavivirus infection in the central nervous system
• Development of novel approaches to restrict flavivirus neurotropism
• Generation of attenuated vaccine candidates against disease caused by highly virulent neurotropic flaviviruses and evaluation of their safety, immunogenicity, and protective efficacy in animal models in preclinical studies, as well as assessment of safety for environment
• Evaluation of safety and immunogenicity of live attenuated vaccine candidates in human clinical trials

Research Group Members

Amber Engel, Olga Maximova, James Speicher, and Natalia Teterina  

Selected Publications

(View list in PubMed.)

Engle AR, Rumyantsev AA, Maximova OA, Speicher JM, Heiss B, Murphy BR, Pletnev AG. The neurovirulence and neuroinvasiveness of chimeric tick-borne encephalitis/dengue virus can be attenuated by introducing defined mutations into the envelope and NS5 protein genes and the 3’ non-coding region of the genome. Virology. 2010 Sep 15;405(1):243-52.

Maximova OA, Faucette LJ, Ward JM, Murphy BR, Pletnev AG. Cellular inflammatory response to flaviviruses in the central nervous system of a primate host. J Histochem Cytochem. 2009 Oct;57(10):973-89.

Blaney JE Jr, Speicher J, Hanson CT, Sathe NS, Whitehead SS, Murphy BR, Pletnev AG. Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic chimeric viruses in mice and rhesus monkeys. Vaccine. 2008 Aug 5;26(33):4150-9.

Pletnev AG, Swayne DE, Speicher J, Rumyantsev AA, Murphy BR. Chimeric West Nile/dengue virus vaccine candidate: preclinical evaluation in mice, geese and monkeys for safety and immunogenicity. Vaccine. 2006 Sep 29;24(40-41):6392-404.

Rumyantsev AA, Murphy BR, Pletnev AG. A tick-borne Langat virus mutant that is temperature sensitive and host range restricted in neuroblastoma cells and lacks neuroinvasiveness for immunodeficient mice. J Virol. 2006 Feb;80(3):1427-39.

Rumyantsev AA, Chanock RM, Murphy BR, Pletnev AG. Comparison of live and inactivated tick-borne encephalitis virus vaccines for safety, immunogenicity and efficacy in rhesus monkeys. Vaccine. 2006 Jan 12;24(2):133-43.

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