Following infection of host cells, vesicular stomatitis virus (VSV) translates its essential proteins at the same time that host protein synthesis is disrupted. This proposal is directed at understanding the molecular mechanisms by which VSV mRNA is translated using the host-cell translation machinery at the same time that host mRNA translation is blocked.
The first aim i s to determine whether VSV mRNA translation is facilitated through cis acting sequences, or whether transcription from the viral genome allows these mRNAs to be translated.
The second aim builds on data which arose from my initial studies here which indicated that VSV infection alters the translation apparatus in a manner that is similar to the cell-stress response.
This aim will expand on my finding that VSV is capable of replicating in cells under stress and will assess VSV's ability to kill hypoxic cancer cells and serve as an anticancer therapy targeting regions of hypoxia. In this second aim I will further test the hypothesis that translation following VSV infection and translation following cell stress are similar. Together these aims form a proposal that studies the mechanisms by which VSV successfully utilizes the host translation apparatus. These project is designed to develop an independent research program focused on discovering more about mechanisms of both viral and host protein translation with an interest in applying the lessons learned to cancer therapy. ? ?
|Connor, John H; Lyles, Douglas S (2005) Inhibition of host and viral translation during vesicular stomatitis virus infection. eIF2 is responsible for the inhibition of viral but not host translation. J Biol Chem 280:13512-9|
|Hantgan, Roy R; Stahle, Mary C; Connor, John H et al. (2004) The disintegrin echistatin stabilizes integrin alphaIIbbeta3's open conformation and promotes its oligomerization. J Mol Biol 342:1625-36|
|Connor, John H; Naczki, Christine; Koumenis, Costas et al. (2004) Replication and cytopathic effect of oncolytic vesicular stomatitis virus in hypoxic tumor cells in vitro and in vivo. J Virol 78:8960-70|