Although the functions of the interactions of CD4 with PLSCR1 and PLSCR4 in the biology of lymphoid or myeloid cells expressing CD4, as well as in the HIV-1 infection process, remain to be elucidated, the demonstration that the CD4 receptor associates directly with PLSCR1 and PLSCR4 may represent a critical point for the understanding of the antiviral activity of SLPI. This evidence concerns the gene SLPI and HIV-1 infection.