Influenza virus replication also impacts on nuclearcytoplasmic trafficking and leads to the nuclear accumulation of host mRNAs [162, 207] . Influenza virus NS1 protein is a major virulence factor that is essential for pathogenesis, because it impairs innate and adaptive immunity by inhibiting host signal transduction and gene expression [208, 209] . NS1 forms a complex with NXF1/TAP, p15/NXT [162] , Rae1, and E1B-AP5, which are components of the mRNA nuclear export machinery (see above). Individual expression of NS1 in 293T cells induces the accumulation of polyadenylated mRNAs in the nucleus, suggesting that the interaction of NS1 with these export factors yields an inactive complex for mRNA export. Influenza virus also induces a strong reduction of Nup98 steady-state levels although the viral mechanisms involved in this process are still unknown [162] . Expression of reporter luciferase mRNA synthesized from a nuclear plasmid is inhibited by NS1. However, this inhibition is overcome by overexpression of NXF1, p15, Rae-1 or Nup98, evidencing the role of NS1 interaction with these factors in the impairment of mRNA nuclear export [162] . Furthermore, mouse cells expressing low levels of Nup98 or/and Rae-1 show greater susceptibility to influenza infection, resulting in a significant increase in cell death and virus production. In addition, mRNAs encoding antiviral factors or immunomodulators such as IRF-1, MHC I and ICAM1 accumulated more in the nucleus of those cells than in cells expressing normal levels of Nup98 or Rae-1 [162] . All these data support the physiological role of NS1 interaction with RNA export factors as well as the reduction of Nup98 levels in influenza pathogenicity. Interestingly, VSV M, influenza NS1 and PV 2A pro expression gives rise to similar effects on mRNA trafficking. All these viral proteins target Nup98 and other components of the cellular machinery involved in nuclear-cytoplasmic trafficking.