Wolfgang Karl Joklik
James B. Duke Professor Emeritus of Medicine
My research is focused on basic studies of the replication cycle of reovirus as a model for understanding the multiplication of rotaviruses, major human pathogens that are the primary cause of death of infants worldwide. We are focusing on three key questions. The first is the nature of the reovirus RNA polymerase/replicase. We have demonstrated that reovirus protein lambda3 is capable of transcribing poly C into poly G; but it fails to transcribe reovirus ss or dsRNA. We are in the process of identifying the cofactors that enable it to do so. Second, we have shown that the major component of the reovirus outer capsid shell is a protein, mu1C, that is translated as a precursor mu1, that is then cleaved to mu1C in the presence of another reovirus protein sigma3. We are attempting to identify the catalytic site that effects this cleavage by studying how these two highly purified proteins interact, on the one hand, and using as substrates model peptides that span the cleavage site. Third, we have shown that reovirus ssRNA is infectious; when lipofected into cells infected with a helper virus particles. We are attempting to manipulate this system into accepting RNA segments engineered so as to identify the signals required for their assortment into the reovirus genome, as well as functional domains of the proteins that they encode.
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