The trimeric envelope glycoproteins (Env) that are displayed on human and simian immunodeficiency viruses (HIV and SIV, respectively) are heterodimers of the transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120). The glycoproteins gp120 and gp41 are synthesized initially as a single gp160 polypeptide that is subsequently cleaved to generate the noncovalently associated gp120/gp41 complex. The conformational changes triggered in trimeric Env upon CD4 binding lead ultimately to fusion of the viral and cell membranes and to delivery of the viral core into infected cells.