34 Translational Reprogramming during Influenza Virus Infection

Abstract

Influenza virus infection is one of the most common human infectious diseases and a worldwide health problem. It is also one of the most dreadful threats for a recurring pandemic, responsible for more than 20 million deaths worldwide in 1918–1919 (the “Spanish” flu). Indeed, the recent outbreaks of H5 influenza viruses in Hong Kong in 1997–1998 gave the world a frightening feeling of déjà vu. Apart from being a medically important viral pathogen, influenza virus serves as an attractive system for studying translational control because it severely impairs the ability of the host to initiate protein synthesis on cellular mRNAs, a phenomenon known as host shutoff. Yet this highly cytopathic virus is able to maintain selective and efficient translation of its own mRNAs in a cap-dependent manner. This requires the infected cell to be translationally proficient so that the processes involved in the protein synthetic pathway remain intact. Furthermore, like many animal viruses, influenza virus has to overcome the host innate antiviral response, of which one important mediator, namely the PKR protein kinase (see Chapters 8 and 13), exerts its effect by arresting global protein synthesis at the translation initiation step. To accomplish these goals, influenza virus has evolved diverse and intricate strategies, ranging from the inhibition of cellular mRNA translation to the preferential translation of viral mRNAs to the inactivation of the PKR protein kinase (Table 1).

STRATEGIES OF HOST SHUTOFF BY INFLUENZA VIRUS
Like other cytopathic viruses, influenza virus dramatically perturbs the normal synthesis of host...