Hijacking of the host-cell response and translational control during influenza virus infection

Influenza virus is a major public health problem with annual deaths in the US of 36,000 with pandemic outbreaks, such as in 1918, resulting in deaths exceeding 20 million worldwide. Recently, there is much concern over the introduction of highly pathogenic avian influenza H5N1 viruses into the human population. Influenza virus has evolved complex translational control strategies that utilize cap-dependent translation initiation mechanisms and involve the recruitment of both viral and host-cell proteins to preferentially synthesize viral proteins and prevent activation of antiviral responses. Influenza virus is a member of the Orthomyxoviridae family of negative-stranded, segmented RNA viruses and represents a particularly attractive model system as viral replication strategies are closely intertwined with normal cellular processes including the host defense and stress pathways. In this chapter, we review the parallels between translational control in influenza virus infected cells and in stressed cells with a focus on selective translation of viral mRNAs and the antagonism of the dsRNA and host antiviral responses. Moreover, we will discuss how the use of genomic technologies such as DNA microarrays and high through-put proteomics can be used to gain new insights into the control of protein synthesis during viral infection and provide a near comprehensive view of virus-host interactions.