Our results demonstrated that: 1) envelope PtdSer can mediate HIV-1 binding via the host’s PtdSer-binding molecule; 2) binding mediated by envelope PtdSer cannot mediate virus infection without expression of CD4 and co-receptors on target cells, most likely due to the lack of activation of fusion activity of gp160; and 3) envelope PtdSer can facilitate HIV-1 infection of CD4 and co-receptor positive cells by facilitating the virus binding step (raw data not shown but available with detailed materials and methods from the corresponding author per request) (summarized in Fig. 2). Here, CD4 is linked to HIV-1 infection.