FIG 6.

A working model for the differential roles of LY6E in HIV-1 infection, a CD4-dependent effect. (A) In low-CD4-expressing cells (such as Jurkat T cells, macrophages, and others), LY6E is associated with CD4 within the lipid raft microdomain, thus promoting its internalization from the plasma membrane; this would result in a decreased CD4 level on the cell surface and therefore impairs virus binding and entry. In this case, the effect of CD4 downregulation by LY6E is predominant relative to its effect on fusion enhancement; therefore, LY6E acts as a negative factor for HIV infection. (B) In high-CD4-expressing cells (PBMCs, SupT1 cells, and others), the effect of LY6E on the downregulating CD4 is minor compared to the LY6E-mediated enhancement of viral fusion. In this case, LY6E functions as a positive factor for HIV-1 infection.