1. Molecular Mechanisms of Negative-Sense RNA Virus Assembly/Budding. Viruses
studied include: Filoviruses (Ebola and Marburg), Arenaviruses (Lassa Fever and Junin), and
Stomatitis and Rabies).
2. Virus-Host Interactions that Modulate Filovirus and Rhabdovirus Assembly/Budding.
3. Innate Immune Defenses against Filoviruses and Rhabdoviruses.
4. Host-Oriented antiviral therapeutics.
Key words: Ebola, Marburg, VSV, Matrix Proteins, VP40, Budding, VLPs, Reverse-Genetics, Virus-Host Interactions, Innate Immunity.
Description of Research
My laboratory is focused mainly on the molecular events that lead to virus assembly and budding. Our model virus systems include vesicular stomatitis virus (a rhabdovirus that causes disease in bovine and equine species), and the filoviruses Ebola and Marburg (emerging, zoonotic pathogens and potential agents of bioterrorism). Our studies are focused on the viral matrix proteins which are the major building blocks of the virus and function to direct virion assembly and budding. We are particularly interested in understanding how these viral matrix proteins interact with host proteins to facilitate the budding process. We are also interested in the host innate immune response to virus infection, and identifying antivirals that can inhibit egress and spread of filoviruses and rhabdoviruses. A second area of study is to utilize reverse-genetics to generate and recover VSV recombinants expressing the surface gB protein of HSV-1 for use in studies to dissect the structure and function of gB during virus-cell fusion. My lab utilizes a wide-array of techniques for these studies such as, virus-like particle (VLP) budding assays, reverse-genetics to generate VSV recombinants, bimolecular complementation, ubiquitination and ISGylation assays, and fluorescence lifetime imaging microscopy (FLIM).
Dr. Yuliang Liu – Senior Postdoctoral Fellow
Dr. Yonggang Qu – Visiting Scientist.
Ms. Sasha Stone – Penn Undergraduate Bio-Engineering Major (Independent Study)
Mr. Benoit Clerc-Renaud – 2011 NIH/Merial Veterinary Scholar
Harty, R. N., Pitha, P. M., and Okumura, A. Antiviral Activity of Innate Immune Protein ISG15. J. Innate Immun. J. Innate Immun. 1: , 2009.Okumura, A. and Harty, R. N. Rabies Virus Assembly and Budding. In: Research Advances in Rabies (Alan Jackson, Ed.) Advances in Virus Research 79: 23-32, 2011.Lu, Jianhong, Qu, Yonggang, Liu, Yuliang, Jambusaria, Rakesh, Han, Ziying, Ruthel, Gordon, Freedman, Bruce D., Harty, Ronald N. Host IQGAP1 and Ebola Virus VP40 Interactions Facilitate Virus-Like Particle Egress journal of virology 87: 7777-7780, 2013.Irie, Takashi, Liu, Yuliang, Drolet, Barbara S., Carnero, Elena, Garcia-Sastre, Adolfo, Harty, Ronald N. Cytopathogenesis of Vesicular Stomatitis Virus Is Regulated by the PSAP Motif of M Protein in a Species-Dependent Manner viruses-basel 4: 1605-1618, 2012.Liu, Yuliang, Stone, Sasha, Harty, Ronald N. Characterization of Filovirus Protein-Protein Interactions in Mammalian Cells Using Bimolecular Complementation journal of infectious diseases 204: S817-S824, 2011.Liu, Yuliang, Harty, Ronald N. Viral and host proteins that modulate filovirus budding future virology 5: 481-491, 2010.Liu, Yuliang, Cocka, Luis, Okumura, Atsushi, Zhang, Yong-An, Sunyer, J. Oriol, Harty, Ronald N. Conserved Motifs within Ebola and Marburg Virus VP40 Proteins Are Important for Stability, Localization, and Subsequent Budding of Virus-Like Particles journal of virology 84: 2294-2303, 2010.Saloura, Vassiliki, Wang, Liang-Chuan S., Fridlender, Zvi G., Sun, Jing, Cheng, Guanjun, Kapoor, Veena, Sterman, Daniel H., Harty, Ronald N., Okumura, Atsushi, Barber, Glen N., Vile, Richard G., Federspiel, Mark J., Russell, Stephen J., Litzky, Leslie, Albelda, Steven M. Evaluation of an Attenuated Vesicular Stomatitis Virus Vector Expressing Interferon-beta for Use in Malignant Pleural Mesothelioma: Heterogeneity in Interferon Responsiveness Defines Potential Efficacy human gene therapy 21: 51-64, 2010.Okumura, Atsushi, Pitha, Paula M., Yoshimura, Akihiko, Harty, Ronald N. Interaction between Ebola Virus Glycoprotein and Host Toll-Like Receptor 4 Leads to Induction of Proinflammatory Cytokines and SOCS1 journal of virology 84: 27-33, 2010.Harty, Ronald N. No exit: Targeting the budding process to inhibit filovirus replication antiviral research 81: 189-197, 2009.