| As obligate intracellular parasites, viruses must co-opt basic cellular processes to enter into host cells and deliver their genomes to the appropriate intracellular site (1). Viral entry steps include attachment of the virus to the cell surface, penetration of the virus into the cell interior, disassembly of the viral capsid, and activation of the viral genetic program. These events are essential for the virus to transition from the extracellular environment to the cellular compartment in which viral transcription and replication occur. Entry steps also play key roles in viral pathogenesis, as these events often determine cell tropism within the infected host.;Mammalian orthoreoviruses (reoviruses) are important models for studies of virus cell entry and the pathogenesis of viral disease. Reovirus entry is initiated by attachment to both carbohydrate and proteinaceous cell-surface receptors. Binding events trigger internalization of virions into endosomes where uncoating takes place. Following removal of the viral outer capsid, viral proteins breach the endosomal membrane, releasing the transcriptionally active core into the cytoplasm. Recent work in our lab and others has defined cellular components necessary for uncoating and membrane penetration in cell culture. However, the role of these cellular factors in vivo is not understood. For my dissertation research, I have investigated the function of endosomal cathepsin proteases, enzymes required for uncoating of the reovirus outer capsid, in reovirus pathogenesis and disease. |
