Role of host proteins in gene expression of nonsegmented negative strand RNA viruses

This chapter reviews the recent progress in the understanding of the role of host proteins in the life cycle of nonsegmented negative strand (ns)RNA viruses. The likelihood that multiple cellular proteins are involved in the regulation of RNA polymerase activity of nsRNA viruses opens avenues for further detailed investigation. Central fields of interest include (1) protein kinases that play a key role in signal transduction and oncogenesis, (2) elongation factors involved in protein biosynthesis, the cytoskeletal framework that regulates cell shape, size, and multiplication, (3) heat shock protein in protein folding and chaperone function, and (4) RNA-binding proteins that mediate essential RNA metabolism have become the central fields of interest. The most pressing issues are to confirm the importance of the implicated molecules, to determine their precise roles, and to delineate their mode of action. Themes of protein kinase-mediated regulation of gene expression are emerging from studies with different nonsegmental nsRNA viral systems. Surprisingly, different kinases were implicated in the activation of their P proteins, and in some cases even related viruses were found to require different protein kinase(s). Thus, it seems that specific cellular protein kinases, depending on their level of expression, may determine tissue tropism and pathogenicity. It is important to learn how these viruses have evolved to interact with specific cellular kinases for the activation of their RNA polymerase activity. Clearly, the next breakthrough will come from elucidation of the three-dimensional structure of the P proteins, which may allow identification of interacting domains and the mechanism of activation of the P protein. © 1997, Academic Press Inc.