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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. Soluble versions of trimeric gp140, either cleaved or uncleaved, are being developed as immunogens to elicit a protective humoral immune response against HIV-1 infection.