Genetic mutations associated with HLH—such as those in familial HLH (PRF1, UNC13D, and STX11 genes), several granule/pigment-abnormality genes (RAB27A, LYST, AP3B1), X-linked lymphoproliferative disease genes (SH2D1A, XIAP), and others such as nlrc4 and cdc42—can significantly influence an individual’s susceptibility to developing HLH in response to viral infections. This evidence concerns the gene NLRC4 and viral infectious disease.