In conclusion, using direct and competitive binding assays, as well as an HIV-1 infection assay, we have provided experimental evidence indicating that the interaction of the HIV-1 glycoprotein gp120 with its cellular coreceptor CXCR4 can be functionally mimicked by peptides presenting essential parts of the binding sites of the two proteins for each other, i.e., the V3 loop of gp120 and the three ECLs of CXCR4. Here, ITIH4 is linked to HIV-1 infection.