Lack of the trans-receptor mechanism of HIV-1 infection: CD4- and coreceptor-independent incorporation of HIV-1-resistant cells into syncytia induced by HIV-1

Human immunodeficiency virus type 1 (HIV-1) infects cells through an interaction of HIV-1 envelope protein with CD4 and an appropriate coreceptor on target cells. This interaction often leads to cell fusion, and formation of syncytia. HIV-1-resistant cells expressing either CD4 or a coreceptor are often surrounding HIV-1-susceptible cells, expressing both CD4 and a compatible coreceptor, in vivo. It is therefore worthwhile to investigate whether these HIV-1-resistant cells could cooperate in HIV-1 infection or cell fusion leading to their incorporation into syncytia. When CD4-positive, coreceptor-negative cells were co-cultured with CD4-negative, coreceptor-positive cells and exposed to HIV-1, HIV-1 infection was not established, indicating that CD4 and the coreceptor expressed on different cell surfaces could not cooperate in HIV-1 entry. However, when HIV-1-resistant cells expressing CD4 or a coreceptor or lacking both were mixed with HIV-1-susceptible cells and inoculated with HIV-1, all these HIV-1-resistant cells were similarly incorporated into syncytia induced by HIV-1, indicating a CD4- and coreceptor-independent incorporation of HIV-1-resistant cells into syncytia. This incorporation was impaired by the transfection of these cells with siRNAs for adhesion molecules. Our study demonstrates that HIV-1-resistant cells can be incorporated into syncytia induced by HIV-1 and this incorporation may partially be mediated through adhesion molecules.