This review highlights some specific HLA alleles that have been associated with protection or with increased risk of HAM/TSP development; KIR2DL2 and IFN-λ3 rs8099917 (GG) polymorphism, associated with HLA class I-restricted, may be involved in the pathogenic mechanism of HIV and HCV infections. The gene discussed is IFNL3; the disease is tropical spastic paraparesis.