Ellie Ehrenfeld, Ph.D.

Chief, Picornavirus Replication Section

Description of Research Program

Our laboratory studies the molecular mechanisms of several aspects of the replication of picornaviruses, a virus family that includes human pathogens such as poliovirus, Coxsackievirus, rhinovirus, and hepatitis A virus. Infection of cells with these viruses leads to major changes in the host cell's intracellular architecture and metabolic activity. Cellular protein and RNA synthesis are inhibited; the intracellular membrane network becomes rearranged into vesicles that surround and provide a scaffold for viral RNA replication complexes; the cellular protein secretory process is disrupted; and cellular proteins are subverted into facilitating viral protein and RNA synthesis. The unique combination of viral and cellular proteins accomplishes a highly efficient production of viral RNA, proteins, and particles.

Using biochemical, biophysical, and genetic approaches, we are studying the activities of individual viral gene products, expressed alone or in combination, in cultured cells and in an in vitro RNA replication system, to dissect their specific roles in the replication process. Interactions of cellular membranes with viral proteins are being analyzed, and the induction of membrane trafficking to generate replication vesicles is being studied. Assays for individual steps in the reaction have been developed and mutations in specific viral proteins have been engineered and analyzed for their effects on individual steps in the replication process.

Memberships

ASV, ASBMB, RNA Society

Research Group Members

Peter Adams, George Belov, Eric Levenson, Natalya Teterina, Don Weaver

Selected Publications

(View list in PubMed.)

Teterina NL, Gorbalenya AE, Egger D, Bienz K, Rinaudo MS and Ehrenfeld E. Testing the Modularity of the Conserved N-terminal Amphipathic Helix in Picornavirus 2C Proteins and Hepatitis C NS5a Protein. Virology, 344:453-467 (2006).

Teterina NL, Levenson E., Rinaudo,MS, Egger D, Bienz K, Gorbalenya A. and Ehrenfeld, E. Evidence for Functional Protein Interactions Required for Poliovirus RNA Replication. J. Virol. 80: 5327-5337 (2006)

Belov, G, Altan-Bonnet, N, Kovtunovych, G. Jackson, CA, Lippincott-Schwartz, J and Ehrenfeld, E. Hijacking Components of the Cellular Secretory Pathway for Replication of Poliovirus RNA. J. Virol. 81: 558-567, 2007.

Supplemental Material

HeLa cells expressing Arf1-GFP fusion were infected with poliovirus and monitored during the course of infection. (Due to size limitations, the movie presented is significantly reduced in size, resolution, and frame rate.)

Windows Media Player, 2.9MB
Quicktime, 2.9MB
Quicktime, 7.7MB
Full video is available upon e-mail request

Interest Groups: RNA Club

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