Virology Faculty Member - James Hogle

James Hogle

Professor of Biological Chemistry and Molecular Pharmacology

Harvard Medical School
BCMP, Bldg. C2, Rm.122
240 Longwood Avenue
Boston, MA 02115
Tel: 617-432-3918
Fax: 617-432-4360
Email: jhogle@hms.harvard.edu



Research in the Hogle lab employs a variety of biophysical, biochemical and molecular approaches to probe the relationship between virus structure and function. The work in the lab is currently focused in three main areas 1) the cell entry pathway of poliovirus and related picornaviruses, 2) herpes virus relication proteins, 3) antiviral design.

1) Although poliovirus and related small icosahedral viruses are relatively simple and arguably the best understood viral pathogens, they must perform a variety of biological functions at various stages of their life cycle, many of which, including cell-entry, remain poorly understood. Understanding the cell entry pathway of simple viruses poses structural questions that span more than six orders of magnitude in scale ranging from the atomic level (tenths of nanometers) to the cellular level (tens of microns). Our studies of poliovirus cell entry therefore employ a multidisciplinary approach, including the use of single molecule techniques to follow the pathways leading to release of the viral genome during normal infection (in collaboration with Xiaowei Zhuang), the development of receptor- decorated liposomes and tethered bilayers as simple model systems for biochemical and structural characterization of the early events during infection, structural studies of soluble and membrane-bound virus-receptor complexes and cell entry intermediates using electron cryoimicroscopy, and electron cryotomography, and structural studies of cell entry intermediates in cells using correlative microscopy (an approach that combines fluorescence microscopy and electron tomography) of both fixed and frozen samples. 2) In collaboration with Don Coen, we have initiated a program of structural studies of essential proteins from herpes viruses. We have recently solved the structure of the processivity factor from herpes simplex virus (UL42) in complex with a peptide from the C-terminus of the catalytic subunit of the polymerase and the processivity factor from cytomegalovirus (UL44) alone and in complex with a peptide from the C-terminus of its polymerase. 3) Our interest in structures of viruses and viral proteins has naturally led us to investigate methods for using the structures to design antiviral drugs.



Last Update: 10/22/2013



Publications

D. Bubeck, D. J. Filman and J. M. Hogle (2005) Cryo-electron microscopy reconstruction of a poliovirus-receptor­membrane complex. Nat Struct Mol Biol 12: 615-8.

D. Bubeck, D. J. Filman, N. Cheng, A. C. Steven, J. M. Hogle and D. M. Belnap (2005) The Structure of the Poliovirus 135S Cell Entry Intermediate at 10-Angstrom Resolution Reveals the Location of an Externalized Polypeptide That Binds to Membranes. J Virol 79: 7745-55.

T. J. Tuthill, D. Bubeck, D. J. Rowlands and J. M. Hogle (2006) Characterization of early steps in the poliovirus infection process: receptor-decorated liposomes induce conversion of the virus to membrane-anchored entry-intermediate particles. J Virol 80: 172-80.

B. A. Appleton, J. Brooks, A. Loregian, D. J. Filman, D. M. Coen and J. M. Hogle (2006) Crystal structure of the cytomegalovirus DNA polymerase subunit UL44 in complex with the C terminus from the catalytic subunit. Differences in structure and function relative to unliganded UL44. J Biol Chem 281: 5224-32.

B. Brandenburg, L.Y. Lee, M. Lakadamyali, M.J. Rust, X. Zhuang, and J. M. Hogle (2007) Imaging poliovirus in live cells. PLoS Biology 5:e183.

M. Bostina, D. Bubeck, C. Schwartz, D. Nicastro, D. J. Filman, and J. M. Hogle (2007) Single particle cryoelectron tomography characterization of the structure and structural variability of poliovirus-receptor-membrane complex at 30 A resolution. J. Struct. Biol. 160: 200-10.



© 2013 by the President and Fellows of Harvard College