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25 To determine whether the virulent mouse-adapted avian H5N2 (Av/ma81) virus20 is sensitive to Mx1, we inoculated B6-Mx1?/? and B6-Mx1+/+ mice with virus (105.5 TCID50 i.n.). All of the virus-infected B6-Mx1?/? mice became severely ill, quickly losing weight (��25% from baseline value), starting at 2 days after infection (dpi) ( Figure?1A). All B6-Mx1?/? mice died within 6 dpi ( Figure?1B). Furthermore, infected B6-Mx1?/? mice exhibited severe pneumonia and liver-like lungs ( Figure?1C and Supplemental Figure?S1), which were associated with high viral titers (peak titer, Selleckchem GPCR Compound Library 4.3 log10 TCID50/g) maintained up to 5 dpi ( Figure?1D). These results demonstrate that the avian H5N2 (Av/ma81) virus is virulent in B6-Mx1?/? mice. 20 In contrast, B6-Mx1+/+ mice showed minimal mean weight loss ( lesions were apparent ( Figure?1, C and D, and Supplemental Figure?S1). Overall, these results demonstrate enhanced resistance of B6-Mx1+/+ mice against the H5N2 virus and show that the Mx1 protein contributes to the suppression of viral replication and promotes protection from lethal AI virus infection. On confirmation of the significant Transferase role of the Mx1 protein in resistance to lethal avian influenza virus infection in B6 mice, we next sought to determine the genes that are differentially regulated between B6-Mx1+/+ and B6-Mx1?/? mice and are therefore associated with Mx1 function during lethal AI virus infection. To this end, lungs were harvested at 1 and 3 dpi from mice infected with the H5N2 (Av/ma81) virus (105.5 TCID50 i.n.). Lungs were also harvested at 4 hpi, to interrogate Fasudil cost differential gene regulation between mouse strains at an early time point of infection. Total RNA was extracted from the lung tissue samples and was subjected to global transcriptional analysis using MouseWG-6 expression bead arrays (Illumina). Differentially regulated genes from B6-Mx1?/? and B6-Mx1+/+ mice were selected based on fold change (greater than twofold difference) as calculated by two-way analysis of variance, as well as statistical significance (P