Purified,Proteolytically Mature HIV Type 1 SOSIP gp140 Envelope Trimers

HIV type 1 (HIV-1) envelope is a noncovalent trimer of gp120–gp41 heterodimers, and its lability has hindered structural studies. SOSIP gp140 is a soluble, proteolytically mature form of the HIV-1 envelope wherein gp120–gp41 interactions are stabilized via a disulfide bond and gp41 contains an additional trimer-stabilizing point mutation. We describe the isolation of a substantially pure preparation of SOSIP gp140 trimers derived from KNH1144, a subtype A isolate. Following initial purification, the only significant contaminant was higher-order gp140 aggregates; however, 0.05% Tween 20 quantitatively converted these aggregates into trimers. The surfactant effect was rapid, dose dependent, and similarly effective for a subtype B SOSIP gp140. Surfactant-treated SOSIP gp140 retained favorable antigenicity and formed compact trimers 12–13 nm in size as determined by electron microscopy. This report provides the first description of homogeneous, cleaved HIV-1 envelope trimers. These proteins may be useful as vaccine immunogens and for studying structure–function relationships within the HIV-1 envelope glycoproteins.