| Modulation cell surface receptor expression and signaling is essential to the survival of many viruses. U24, a conserved protein encoded by roseoloviruses, downregulates the surface expression of the T cell receptor (TCR), a protein complex essential to T cell activation and the generation of an adaptive immune response. In the presence of U24, the TCR is endocytosed but is not recycled back to the plasma membrane and accumulates in early and late endosomes. T cells expressing U24 demonstrate an inability to become activated by antigen presenting cells potentially acting to limit viral reactivation.;In addition, U24 expression has been used to study host cellular processes. The mechanism of post translational insertion of tail anchored proteins has been poorly understood. I present evidence that U24 is a tail anchored protein that depends on TRC40/Asna-1 for its function. In addition, a proline-rich region conserved in U24 sequences suggests that a WW domain containing protein regulates early endosomal recycling. Overall, this dissertation seeks to validate the study of viral proteins as a means to uncover host biological processes. |
