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Associate Professor

Contact Information:
Email: Office Phone: 318-675-5771
Laboratory Phone: 318-675-5773
Office Fax: 318-675-5764

Education/Training:
Postdoctoral Study, The University of North Carolina at Chapel Hill
Ph.D., Molecular Virology, 1998, The University of North Carolina at Chapel Hill
B.A., Microbiology, 1992, Southern Illinois University

Major Research Interest:
Molecular Pathogenesis of Arboviruses

The goal of my laboratory is to define the host and viral factors that determine the success or failure of the innate immune response to infection with arthropod-borne viruses.  The specific approach is to examine at the single cell level, the molecular mechanisms that determine host cell permissivity to the alphaviruses (e.g., Sindbis virus, Venezuelan equine encephalitis virus, eastern equine encephalitis virus and Ross River virus) and the contribution of replication in specific cells to the pathogenesis of viral disease. Upon introduction into a susceptible host, alphaviruses initially replicate within cells of the dendritic cell (DC) and macrophage lineages.  In young animals, this replication is unrestrained and leads to induction of a toxic proinflammatory cytokine response.  However, in adults virus replication and cytokine induction are restricted by one or more as yet uncharacterized mechanisms. These mechanisms likely involve changes in host cell permissivity to virus infection.  Ongoing studies include: determination of the relationship between infection of DC/macrophage and induction of the systemic inflammatory response, identification and characterization of cellular receptors that promote virus infection and identification of host innate immune mechanisms that control virus replication within individual cells.  We have recently determined that some, if not most alphaviruses attach to C-type lectins (host cell carbohydrate-binding proteins) during infection of DC and macrophages in vitro and are currently investigating the role of these receptors in targeting virus particles to specific cells in vivo.  In collaboration with Dr. Kate Ryman, we have found that the interferon-mediated innate antiviral system also plays an important role in determining which cells are productively infected.  We are currently dissecting the individual molecular pathways involved in interferon-mediated control of virus replication and their relationships to cell infection in vivo.

Representative Publications:

 

Klimstra, W.B., E.M. Nangle, M.S. Smith, A.D. Yurochko and K.D. Ryman. 2003. DC-SIGN and L-SIGN can act as attachment receptors for alphaviruses and distinguish between mosquito cell- and mammalian cell-derived viruses.  J. Virol. 77:12022-12032.

Ryman, K.D., K.C. Meier, E.M. Nangle, S.L. Ragsdale, N.L. Korneeva, R.E. Rhoads M.R. MacDonald and W.B. Klimstra. 2005. Sindbis virus translation is inhibited by a PKR/RNase L-independent effector induced by IFN-α/β priming of dendritic cells.  J. Virol. 79:1487-1499.

 

Klimstra, W.B., J.C. Williams, K.D. Ryman and H.W. Heidner. 2005. Targeting Sindbis virus-based vectors to Fc receptor-positive cell types.  Virology. 338:9-21.

Ryman, K.D., C.L. Gardner, K.C. Meier, C.A. Biron, R.E. Johnston and W.B. Klimstra. 2007. Early restriction of Alphavirus replication and dissemination contributes to age-dependent attenuation of systemic hyperinflammatory disease. J. Gen. Virol., 88:518-529.

Ryman, K.D., C.L. Gardner, C.L. Wyza, K.C. Meier, J.M. Thompson and W.B. Klimstra. 2007. Heparan-sulfate binding can contribute to the neurovirulence of neuroadapted and non-neuroadapted Sindbis viruses. J.Virol. 81:3563-3573.

Zhang, Y., C.W. Burke, K.D. Ryman and W.B. Klimstra. 2007. Identification and characterization of interferon-induced proteins that inhibit alphavirus replication.  J. Virol. 81:11246-11255.

Ryman, K.D., K.C. Meier, C.L. Gardner and W.B. Klimstra. 2007. Non-pathogenic Sindbis virus causes viral hemorrhagic fever when antiviral activities of alpha/beta and gamma interferon are absent. Virology. ePub ahead of print.

 

 

 


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