title: Purified, proteolytically mature HIV type 1 SOSIP gp140 envelope trimers.
abstract: 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.
authors.affiliation: Progenics Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
authors.forename: Sai Prasad N
authors.initials: SP
authors.lastname: Iyer
authors.forename: Michael
authors.initials: M
authors.lastname: Franti
authors.forename: Ammie A
authors.initials: AA
authors.lastname: Krauchuk
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Fisch
authors.forename: Amadou A
authors.initials: AA
authors.lastname: Ouattara
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Roux
authors.forename: Laura
authors.initials: L
authors.lastname: Krawiec
authors.forename: Antu K
authors.initials: AK
authors.lastname: Dey
authors.forename: Simon
authors.initials: S
authors.lastname: Beddows
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Maddon
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
authors.forename: William C
authors.initials: WC
authors.lastname: Olson
mesh_terms: D015686:Gene Products, env / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D008854:Microscopy, Electron; D020836:Protein Structure, Quaternary; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D015686:Gene Products, env; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1