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.
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:
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.
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:
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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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.
Hideki Ebihara, Ph.D., Chief, Molecular Virology and Host-Pathogen Interaction Unit, LVLogan Banadyga, Ph.D., Postdoctoral Visiting FellowAllison Groseth, Ph.D., Staff Scientist (VP)McKenzie Quinn, Post-baccalaureate IRTACarla Weisend, Molecular BiologistBrandi Williamson, MicrobiologistVeronica Vine, Post-baccalaureate IRTASatoko Yamaoko, Ph.D., Postdoctoral Visiting Fellow
Tsuda Y, Hoenen T, Banadyga L, Weisend C, Ricklefs SM, Porcella SF, Ebihara H. An Improved reverse genetics system to overcome cell-type-dependent Ebola virus genome plasticity. J Infect Dis. 2015 Mar 24. Epub ahead of print.
Groseth A, Wollenberg KR, Mampilli V, Shupert T, Weisend C, Guevara C, Kochel TJ, Tesh RB, Ebihara H. Spatiotemporal analysis of Guaroa virus diversity, evolution, and spread in South America. Emerg Infect Dis. 2015 Mar;21(3):460-3.
Matsuno K, Weisend C, Kajihara M, Matysiak C, Williamson BN, Simuunza M, Mweene AS, Takada A, Tesh RB, Ebihara H. Comprehensive molecular detection of tick-borne phleboviruses leads to the retrospective identification of taxonomically unassigned bunyaviruses and the discovery of a novel member of the genus phlebovirus. J Virol. 2015 Jan;89(1):594-604.
Ebihara H, Zivcec M, Gardner D, Falzarano D, LaCasse R, Rosenke R, Long D, Haddock E, Fischer E, Kawaoka Y, Feldmann H. A Syrian golden hamster model recapitulating ebola hemorrhagic fever. J Infect Dis. 2013 Jan 15;207(2):306-18.
Groseth A, Marzi A, Hoenen T, Herwig A, Gardner D, Becker S, Ebihara H, Feldmann H. The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo. PLoS Pathog. 2012;8(8):e1002847.
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.
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Last Updated June 24, 2015