Gary R. Whittaker - Cornell Veterinary Medicine

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Gary R. Whittaker

Professor of Virology

Cornell University College of Veterinary Medicine
C4 127 Veterinary Medical Center
E-mail: grw7@cornell.edu
Phone: 607-253-4019

Ph.D. (University of Leeds, UK)

Whittaker Lab home page

Dr. Whittaker is a Professor in the Department of Microbiology and Immunology and has been associated with the department since 1996. He received a bachelor's degree in Biochemistry and his Ph.D. in Microbiology from Leeds University U.K. where he studied the molecular biology and biochemistry of equine herpesvirus. He obtained postdoctoral training at Yale University in the laboratory of Dr. Ari Helenius, studying the cell biology of influenza virus replication. Dr Whittaker's laboratory is focused on the entry of influenza viruses, rhaboviurses and coronaviruses into host cells and is funded by research grants from the National Institutes of Health.

Research Interests | Graduate Fields | Lab Members | Related Links | Selected References

Research Interests

Current research interests of the Whittaker lab focus on how enveloped viruses enter host cells. The laboratory focuses on three principal viral systems; 1) influenza virus - including avian and equine influenza, 2) coronaviruses - including avian infectious bronchitis virus, feline infectious peritonitis virus (FIPV) and the SARS-coronavirus, and 3) Rhabdoviruses - vesicular stomatitis virus (VSV) and viral hemorrhagic septicemia virus (VHSV). All of these viruses enter cells following receptor binding and fusion of the virus envelope with the cell membrane. The focus of the laboratory is on how receptor utilization interfaces with the route of endocytosis, the proteolytic priming of the envelope protein and the pH-dependent activation of membrane fusion. We utilize a variety of techniques, encompassing molecular and cell biology and biochemistry, as well as structural studies of the viral fusion proteins.

Virus entry
Entry of influenza viruses.
We are studying the entry mechanism of influenza virus into its host in order to gain information on the pathogenic properties of the virus. Specifically, we are studying the route of endocytosis and the cell signaling pathways activated during virus entry, with the goal of identifying novel antiviral targets, and deciphering any possible co-receptor usage by the virus. From a structural point of view we are interested in the changes that occur in the viral hemagglutinin (HA) molecule that might account for different pathogenic properties as viruses emerge into new species (e.g avian-equine or avian human) and well as how the virus adapts to its new host.

corona virus
Entry of coronaviruses.
We have recently developed the avian virus infectious bronchitis virus (IBV) as a system to study coronavirus entry. We have developed fluorescence dequenching assays of viral fusion to show the role of low pH for entry of IBV, and are applying these techniques to other members of the Coronaviridae. With IBV as a model, we are exploring the process of fusion activation of the SARS-coronavirus, as well as feline infectious peritonitis virus (FIPV), in order to gain molecular insight into the pathogenesis of these deadly viruses.

rhabdovirus
Entry of rhabdoviruses.
Using the information provided by the recent crystal structure of the vesicular stomatitis virus fusion (G) protein, we are carrying out a mutagenesis study to determine the critical amino acids within the fusion domain of VSV G, as well as the related fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV).

Graduate Fields

Dr. Whittaker is a member of the following Graduate Fields:

Biochemistry, Molecular & Cell Biology
Comparative Biomedical Sciences
Immunology and Infectious Disease
Microbiology
Pharmacology

Lab Members

Jean Millet, Postdoctoral Associate
Michele Bialecki, Graduate Student
Yueting Zhang, Graduate Student
Victor Tse, Graduate Student
Beth Licitra, Graduate Student
Nadia Chapman, Technician
Wendy Wingate, Technician
Misty Pocweirz, Technician

Related Links

Program in Virology at Cornell University
Los Alamos Influenza Database
CDC Influenza Homepage
Influenza bibliography - NIMR
National Campaign for Influenza Prevention: Preventinfluenza.org
Intracellular trafficking of influenza virus: clinical implications for molecular medicine (pdf file)
All the Virology on the WWW

Selected References

Sun X, Tse LV, Ferguson AD, Whittaker GR. (2010). Modifications to the hemagglutinin cleavage site control virulence of a neurotropic H1N1 influenza virus. J Virol. Jun 16. [Epub ahead of print]

Belouzard S, Madu I, Whittaker GR. (2010). Elastase-mediated activation of the SARS coronavirus spike protein at discrete sites within the S2 domain. J Biol Chem. May 27. [Epub ahead of print]

Regan AD, Ousterout DG, Whittaker GR. (2010). Feline lectin activity is critical for the cellular entry of feline infectious peritonitis virus. J Virol. May 19. [Epub ahead of print]

Belouzard S, Chu VC, Whittaker GR. (2009). Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci USA. 106:5871-5876.

Roth, S.L. and Whittaker, G.R. (2011). Promotion of vesicular stomatitis virus fusion by the endosome-specific phospholipid bis(monoacylglycero)phosphate (BMP). FEBS Lett. 585: 865-869.

Zhang, Y., Buckles, E.L. and Whittaker, G.R. (2012). Expression of the C-type lectins DC-SIGN or L-SIGN alters host cell susceptibility for the avian coronavirus, infectious bronchitis virus. Vet Microbiol. 2012 Jan 17. [Epub ahead of print]. PMID: 22340967.