Induction of the type I interferon response during influenza infection appears to be important in both human and mouse models, as evidenced by the increased expression of genes including Irf1, Ifi202, Oas1, and Mx1 in mouse microarray studies [73] [74] [75] (reviewed in [76] ). This is consistent with the observation that viral evasion and attenuation of the IFN pathway contributes to H5N1 pathogenesis in humans and suggests potential targets for genetic studies [75, 77] . A strong target for analysis includes the myxovirus resistance (Mx) gene, which encodes interferon-induced antiviral proteins that inhibit viral RNA transcription and consequently confer influenza resistance in mouse lines with functional Mx1 alleles [78] . Polymorphisms in swine Mx genes have also been associated with influenza susceptibility [79] and multiple SNPs in the human MxA gene have been associated with variability in IFN responsiveness in Hepatitis C infection [80] and SARS susceptibility [38] [39] [40] (Table 2) . Specifically, the −123C/A promoter SNP associated with SARS protection correlates with increased basal MxA expression, leading the authors to speculate that −123 genotype may be an important determinant of H5N1 susceptibility [39] . Although human MxA protein has been shown to inhibit influenza replication [81] , no studies have looked for an association between MxA SNPs and H5N1 disease outcome or susceptibility. Because MxA is located on chromosome 21, studies have compared susceptibility to respiratory infections between wild-type and trisomy 21 patients (who exhibit increased MxA expression), but found greater susceptibility among the trisomy 21 group [82] . This group of patients is known to suffer from a multilevel T-cell dysfunction, however, making the role of MxA in respiratory immunity somewhat unclear.