): This application studies the mechanism which cytopathic retroviruses kill their target cells and how this induction of cell death relates to viral pathogenesis in vivo. These studies focus on the avian leukosis virus-B (ALV), whose receptor, TVB, is a functional death receptor in the TNFR-family. Binding of ALV-B Env to the TVB receptor can lead to cell death.
Five specific aims are proposed. The first examines whether the TVB receptor plays a direct role in cell-killing following infection by cytopathic subgroups of ALV. This will be tested using dominant negative forms of the receptor. The second examines the role of Nf-kappaB in the signaling pathway. The third examines whether cells chronically infected with ALV-B are protected against TVBL-induced death.
The fourth aim studies whether viral superinfection contributes to the cytopathic effects. The fifth aim studies a variant of ALV-A, the avian hemangioma virus, which induces cell-killing. These studies will identify the cell death pathway induced possibly through the TVA receptor.
