WHAT HAPPENS INSIDE LENTIVIRUS OR INFLUENZA-VIRUS INFECTED-CELLS - INSIGHTS INTO REGULATION OF CELLULAR AND VIRAL PROTEIN-SYNTHESIS

Efficient manipulation of the regulatory mechanisms controlling host c ell gene expression provides the means for productive infection by ani mal viruses. Upon infecting the host cell, Viruses must: (i) bypass th e cellular antiviral defense mechanisms to prevent the translational b locks imposed by the interferon pathway; and (ii) effectively ''hijack '' the host protein synthetic machinery into mass production of virion protein components. The multicomponent regulatory nature of cellular gene expression has provided the means of selecting for a diverse rang e of mechanisms utilized by animal Viruses to ensure that replication efficiency is maintained throughout the virus life cycle. One importan t research component of the careful examination of gene regulation is those studies that focus on elucidating the mechanisms by which viruse s control mRNA translation during host cell infection. Much of the wor k in our laboratory has focused on elucidating the strategies by which human immunodeficiency virus type 1 and influenza virus regulate prot ein synthesis during infection. Here we describe the ways in which the se two distinctly different RNA Viruses ensure the selective and effic ient translation of their viral mRNAs in infected cells. These strateg ies include circumvention of the deleterious effects associated with a ctivation of the interferon-induced protein kinase, PKR. Herein we des cribe our methodologies designed to elucidate the translational regula tion in cells infected by these viruses. We conclude with a brief summ ary of new directions, utilizing these methods, taken toward understan ding the translational control mechanisms imposed by these viral syste ms, and how our studies of virally infected cells have allowed us to i dentify growth-regulating components of normal, uninfected cells. (C) 1997 Academic Press.