The Nucleoporin Nup96 Is Required for Proper Expression of Interferon-Regulated Proteins and Functions

Nup98 and Nup96 are components of the nuclear transport machinery and are induced by interferons (IFN). Nup98 is a constituent of an mRNA export pathway that is targeted by viruses and regulated by IFN. However, the role of Nup96 in IFN-related mechanisms has not been established. To investigate the function of Nup96 in vivo, we generated Nup96 +/− mice that express low levels of Nup96, as Nup96 −/− mice are lethal. The Nup96 +/− mice presented selective alterations of the immune system, which resulted in downregulation and impaired IFN α- and γ-mediated induction of MHC I and IFNγ induction of MHC II, ICAM-1, and other proteins. Frequency of TCRαβ+ and CD4+ T cells, which depends on MHC function, is reduced in NUP96 +/− mice. Upon immunization, Nup96 +/− mice showed impaired antigen presentation and T cell proliferation. Nup96 +/− cells and mice were highly susceptible to viral infection, demonstrating a role for Nup96 in innate and adaptive immunity