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Hideki Ebihara, Ph.D.
Building 28, Room 2A130
903 South 4th Street.
Hamilton, MT 59840-2932
Phone: 406-375-7419
ebiharah@niaid.nih.gov

Laboratory of Virology

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Hideki Ebihara, Ph.D.

Photo of Hideki Ebihara

Chief, Molecular Virology and Host-Pathogen Interaction Unit, LV

Major Areas of Research

  • Molecular determinants of filovirus virulence in animals
  • Role of Ebola virus proteins in viral pathogenesis and life cycle
  • Identification of host cellular factors essential for Ebola virus replication
  • Molecular characterization of pathogenic bunyaviruses that cause disease in humans and animals
  • Identification of bunyavirus host range and virulence determinants
  • Mechanisms of bunyavirus evolution

 

 

Program Description

Our lab endeavors to better understand the molecular determinants of virulence and host range for several highly pathogenic RNA viruses. In particular, our research focuses on the molecular virology of filoviruses—including Ebola virus and Marburg virus—and bunyaviruses, specifically the orthobunyaviruses, phleboviruses, and taxonomically ungrouped bunyaviruses.

Molecular basis of host-filovirus interactions in pathogenesis

Viral hemorrhagic fevers caused by Ebola virus (EBOV) and Marburg virus (MARV) are among the most severe infectious diseases in humans, and no licensed vaccines or effective therapeutics are currently available. To develop effective treatments for these diseases, it is necessary to better understand the mechanisms of viral and host interactions at the molecular and cellular levels and how these interactions contribute to the in vivo pathogenic process. We are therefore working to elucidate the roles that filoviral proteins play in the viral replication cycle and pathogenesis. Ongoing work includes the following:

  • Characterization of the molecular determinants of EBOV virulence and adaptation in rodents
  • Elucidation of the roles that viral proteins play in the virus replication cycle and pathogenesis and identification of host cellular factors essential to the virus replication cycle
  • Identification of interactions between viral and host cellular proteins and the molecular characterization of these interactions
  • Characterization of the mechanisms that govern EBOV cellular tropism and its contribution to virulence

Notably, in all aspects of our research, our lab takes full advantage of filovirus reverse genetics in order to decipher host-pathogen interactions with molecular detail.

Molecular determinants of human pathogenic bunyavirus virulence and evolution

The Bunyaviridae is the largest family of RNA viruses, comprising five genera (Orthobunyavirus, Hantavirus, Phlebovirus, Nairovirus, and Tospovirus) and containing more than 350 viruses. Members of the Bunyaviridae are found worldwide, and their host range is very broad, including arthropods, mammals (including humans and bats), birds, and even plants. Since bunyaviruses possess a genome consisting of three negative-strand RNA segments, the evolution of bunyaviruses is complex—being driven by antigenic drift (accumulation of mutations), antigenic shift (genome segment reassortment), and virus/host interactions—making it difficult to understand the mechanisms of biogenesis and emergence/re-emergence of these highly pathogenic viruses.

Orthobunyavirus, the largest genus within the bunyavirus family, comprises a group of globally distributed arthropod-borne viruses that have the potential to cause serious disease in humans and animals, including encephalitis and hemorrhagic fever. Nevertheless, relatively little is known about the genetics and molecular biology that underlies the emergence or re-emergence of these viruses. Our goal, therefore, is to elucidate the molecular determinants that contribute to the virulence of orthobunyaviruses and their emergence. Ongoing work includes the following:

  • Characterization of the mechanism behind virulence acquisition in Ngari virus, a novel re-assortant orthobunyavirus that causes hemorrhagic fever in humans
  • Identification and characterization of the molecular determinants of host range in Simbu serogroup orthobunyaviruses
  • Molecular characterization of uncharacterized orthobunyaviruses and taxonomically ungrouped bunyaviruses with the potential to cause human disease

Research on the filovirus and bunyavirus projects is performed in a state-of-the-art facility under biosafety level 2, 3, and 4 conditions using a variety of molecular tools, including reverse genetics, molecular cloning and mutagenesis, next-generation sequencing, immunofluorescence, immunoprecipitation, flow cytometry, and signal transduction assays.

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Biography

Hideki Ebihara received his Ph.D. in virology and molecular biology in 2001 from Hokkaido University, Japan, where he studied the pathogenesis and genetic determinants of virulence of hantaviruses, which cause hemorrhagic fever with renal syndrome in humans. From 2001 to 2003, Hideki completed postdoctoral research studying the molecular basis of Ebola virus pathogenesis at the School of Veterinary Medicine, University of Wisconsin-Madison. He continued his training first as a postdoctoral fellow (2003–2007) and then as a research associate (2007–2009) with the Institute of Medical Science, University of Tokyo, performing research on the molecular biology and pathogenesis of Ebola, Marburg, and hantaviruses as part of the special pathogens program of the National Microbiology Laboratory at the Public Health Agency of Canada in Winnipeg in the laboratory of Dr. Heinz Feldmann. Dr. Ebihara was recruited to the National Institutes of Health in 2009 as a staff scientist in the Laboratory of Virology at Rocky Mountain Laboratories. In 2010, he established his own laboratory as a tenure-track investigator, studying the molecular mechanisms that underlie the pathogenesis of highly pathogenic human and animal RNA viruses.

Research Group

Hideki Ebihara, Ph.D., Chief, Molecular Virology and Host-Pathogen Interaction Unit, LV
Logan Banadyga, Ph.D., Postdoctoral Visiting Fellow
Allison Groseth, Ph.D., Staff Scientist (VP)
Keita Matsuno , D.V.M, Ph.D., Postdoctoral Visiting Fellow
Carla Weisend, Molecular Biologist
Brandi Williamson, Microbiologist
Satoko Yamaoko, Ph.D., Postdoctoral Visiting Fellow

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Selected Publications

Safronetz D, Zivcec M, Lacasse R, Feldmann F, Rosenke R, Long D, Haddock E, Brining D, Gardner D, Feldmann H, Ebihara H. Pathogenesis and host response in Syrian hamsters following intranasal infection with Andes virus. PLoS Pathog. 2011 Dec;7(12):e1002426.

Ebihara H, Rockx B, Marzi A, Feldmann F, Haddock E, Brining D, LaCasse RA, Gardner D, Feldmann H. Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus. J Infect Dis. 2011 Nov;204 Suppl 3:S991-9.

Ebihara H, Theriault S, Neumann G, Alimonti JB, Geisbert JB, Hensley LE, Groseth A, Jones SM, Geisbert TW, Kawaoka Y, Feldmann H. In vitro and in vivo characterization of recombinant Ebola viruses expressing enhanced green fluorescent protein. J Infect Dis. 2007 Nov 15;196 Suppl 2:S313-22.

Kobasa D, Jones SM, Shinya K, Kash JC, Copps J, Ebihara H, Hatta Y, Halfmann P, Hatta M, Feldmann F, Alimonti JB, Fernando L, Li Y, Katze MG, Feldmann H, Kawaoka Y. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature. 2007 Jan 18;445(7125):319-23.

Ebihara H, Takada A, Kobasa D, Jones S, Neumann G, Theriault S, Bray M, Feldmann H, Kawaoka Y. Molecular determinants of Ebola virus virulence in mice. PLoS Pathog. 2006 Jul;2(7):e73.

Ebihara H, Groseth A, Neumann G, Kawaoka Y, Feldmann H. The role of reverse genetics systems in studying viral hemorrhagic fevers. Thromb Haemost. 2005 Aug;94(2):240-53.

Visit PubMed for a complete publication listing.

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Last Updated June 30, 2014

Last Reviewed October 17, 2012