Although a precise mechanism by which HLA-DRB1*0401 expression results in high immune reactivity was not fully clarified, studies in transgenic immunocompetent mice challenged with H1N1 Influenza virus suggested that the intracellular trafficking of HLA-DRB*0401 occurs through the late endosome/lysosomes, resulting in a superior output of innate responses for clearance of virus infections than the non-protective HLA-DRB*0402 haplotype [33]. Here, HLA-DRB1 is linked to viral infectious disease.