Genetic Polymorphisms of HLA and HLA-related Proteins: Implications on Dengue Virus Infection

Abstract

Dengue diseases pathogenesis is not yet completely understood. Several human immunities are controlled by the expression of human leukocyte antigen (HLA) and expressions of HLA molecules are increased in dengue viral (DENV) infection. The role of cytotoxic T lymphocyte recognizing DENV epitopes presented by the HLA is the basis for immunity of DENV infection. The genes encoding classical HLA class I (HLA-A, -B, -C) and class II (HLA-DR, DQ and DP) are the most polymorphic in the human genome, and specific polymorphisms in human HLA gene regions influence peptide epitope binding. Here we have reviewed the implication of HLA and HLA-related gene polymorphisms on DENV infection susceptibility, protection and severity. We found several studies have identified HLA alleles associated with DENV infection susceptibility and severity such as A*0207, A*1, A*2, A*24, A*31, B blank, B*13, B*40, B*46, B*51, B*52, B*53, B*57, DR1, DRB1*08, DRB1*12, DRB1*15 and TNF-α i?½308A allele. Whereas some HLA alleles such as A*0203, A*03, A*29, A*33, B*13, B*14, B*15, B*18, B*44, B*49, B*52, B*62, B*76, B*77, DRB1*0901, DRB1*02, DRB1*03, DRB1*04, and DRB1*07 are associated with DENV infection protection. In addition, HLA class III and HLA-related proteins - mayor histocompatibility complex class I chain-related protein A and B (MICA and MICB) and lymphotoxin-alpha (LTA) - also associated with DENV infection. In summary, HLA and several HLA-related proteins clearly play important roles on DENV infection susceptibility, protection and severity.