HIV-1 infection begins with binding of gp120, through CD4bs and CoRbs, to the primary receptor CD4 and the co-receptor, CCR5 or CXCR4, on the target cell, triggering the formation of the 6-HB fusion core structure by CHR and NHR in gp41.36 Like sCD4 and mD1.22, 2Dm2m and 4Dm2m can bind to the CD4bs on gp120 to trigger the premature conformational change of gp120, resulting in the exposure of CoRbs on gp120, which can be bound by the m36.4 domain in 2Dm2m and 4Dm2m. Here, ITIH4 is linked to HIV-1 infection.