Office Phone: 318-675-6684
Laboratory Phone: 318-675-5773
Office Fax: 318-675-5764
Postdoctoral Study, University of North Carolina at Chapel Hill
Ph.D. Virology, 1995, University of Surrey, England
B.Sc. Microbiology, 1991, University of Surrey, England
Major Research Interests:
Host responses to mosquito-borne virus infections
Our research focuses on developing a better understanding of the way in which the early virus-host interaction shapes the outcome of infection. We study enveloped RNA viruses from the families Flaviviridae and Togaviridae , many of which are classified as potential agents of biowarfare/bioterrorism and emerging infectious disease because they are extremely pathogenic in humans, but typically have no effective antivirals or licensed vaccines. As o ur understanding of the host-pathogen interaction increases, we believe it will be possible to design live-attenuated virus strains that can be used as vaccines.
We are attacking this problem from two directions:
1) By studying a highly successful live-attenuated vaccine, we hope to gather information that will be useful for the design of other vaccines in the future. A lthough the 17D yellow fever virus vaccine is highly efficacious, molecular mechanisms controlling its attenuation and immunogenicity are poorly understood. Our long-term goals are to reveal which of the mutations accumulated in the 17D genome are attenuating in vivo and determine their effect(s) on early virus-host interactions, eliciting an YFV-specific protective immune response after 17D immunization.
2) By determining and disabling the mechanisms of innate immune evasion utilized by a pathogenic virus, we hope to develop live-attenuated vaccine candidates. To counter the host's potent innate immune system, many pathogenic viruses have developed diverse mechanisms of evasion/antagonism. We are investigating the way(s) in which eastern equine encephalitis virus overcomes the host's antiviral response with the goal of developing an immunogenic, but attenuated strain.
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 and entry receptors for alphaviruses and distinguish between mosquito cell- and mammalian cell-derived virus. Journal of Virology, 77: 12022-12032.
Ryman, K.D., W.B. Klimstra and R.E. Johnston. (2004). Sindbis virus variants incorporating uncleaved PE2 are attenuated in neonatal mice, but mutate rapidly to a cleavage-competent, virulent phenotype. Virology, 322: 1-12 .
Mutebi, J.-P., R.C.A. Rijnbrand, H. Wang, K.D. Ryman, E. Wang, L.D. Fulop, R. Titball, and A.D.T. Barrett. Genetic relationships and evolution of genotypes of yellow fever virus and other members of the yellow fever virus group within the Flavivirus genus. Journal of Virology, 78: 9652-9665.
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- a / ß priming of dendritic cells. Journal of Virology, 79: 1487-99.
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.
Mutebi, J.-P., R.C.A. Rijnbrand, H. Wang, K.D. Ryman, E. Wang, L.D. Fulop, R. Titball and A.D.T. Barrett. (2004). Genetic relationships and evolution of genotypes of yellow fever virus and other members of the yellow fever virus group within the Flavivirus genus. Journal of Virology. 78:9652-9665.
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. Journal of Virology, 79:1487-99.
Ryman, K.D., C.L. Gardner, C.W. Burke, K.C. Meier, J.M. Thompson and W.B. Klimstra. (2007). Heparan sulfate binding can contribute to the neurovirulence of neuroadapted and nonneuroadapted Sindbis viruses. Journal of Virology, 81:3563-73.
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. Journal of General Virology, 88:518-29.
Ryman, K.D., K.C. Meier, C.L. Gardner, P.A. Adegboyega and W.B. Klimstra. (2007). Non-pathogenic Sindbis virus causes hemorrhagic fever in the absence of alpha/beta and gamma interferons. Virology, Epub ahead of print.