21 Translational Control in Cells Infected with Influenza Virus and Reovirus

Abstract

The two RNA viruses, influenza virus and reovirus, utilize dramatically distinct tactics to optimize the translation of viral messenger RNAs. Presented here is a comprehensive review of the strategies used by these two virus groups to ensure both the selective and efficient synthesis of viral proteins. Among other topics are a discussion of the virus-induced “host shutoff” and documentation of the mechanisms by which influenza virus and reovirus down-regulate the double-stranded RNA (dsRNA)-activated, interferon-induced protein kinase, PKR.

INFLUENZA VIRUS
Influenza virus is an enveloped, negative-stranded segmented RNA virus that causes a disease which is responsible for up to 70,000 deaths a year in the United States and in the worst epidemic years, has killed 20,000,000 worldwide. It is a highly cytopathic virus that interferes dramatically with host macromolecular synthesis. Unlike most nononcogenic RNA viruses, the influenza replicative cycle includes both a nuclear and cytoplasmic phase (Krug et al. 1989), and this has a definite influence on the translational strategies of the virus. In the early 1970s, it was recognized that a shutoff of host-cell protein synthesis occurs at times when viral proteins are maximally made (Lazarowitz et al. 1971; Skehel 1972). What was not appreciated at the time were the numerous and complex strategies required by influenza virus to accomplish these goals (Garfinkel and Katze 1993b, 1994). In terms of translational control, influenza virus has two major objectives, neither of which is unique to this virus (see Mathews, this volume): (1) to selectively translate viral mRNAs and stop the translation...