The researchers show that alpha-defensin-1 fights HIV in two different ways. Without serum (the watery portion of blood that remains when blood cells are removed) and under conditions where viral burden is low, alpha-defensin-1 directly inactivates HIV virus. When serum is present, alpha-defensin-1 acts on vulnerable cells to block HIV infection at the stage when the virus is taken up by the cell and begins replicating itself and integrating into the host. The authors also show that the way alpha-defensin-1 blocks HIV infection in cells is by inhibiting a CD4+ cell-signaling molecule called PKC.
The finding that alpha-defensin-1 acts on both the virus and the cell offers insights into the function of alpha-defensin-1 in innate immunity against HIV. In addition, this study provides a basis to develop defensin-like drugs for prevention of HIV and for therapeutic use in patients who are already infected.