title: The impact of envelope glycoprotein cleavage on the antigenicity, infectivity, and neutralization sensitivity of Env-pseudotyped human immunodeficiency virus type 1 particles.
abstract: Endoproteolytic processing of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoproteins is an obligate part of the biosynthetic pathway that generates functional, fusion-competent Env complexes, which are then incorporated into infectious virions. We have examined the influence of cleavage on Env-specific antibody reactivity, Env incorporation into pseudovirions, and the infectivity and neutralization sensitivity of Env-pseudotyped viruses. To do so, we have used both incompletely processed wild-type (Wt) Env and engineered, cleavage-defective Env mutants. We find that there is no simple association between antibody reactivity to cell surface-expressed Env, and the ability of the same antibody to neutralize virus pseudotyped with the same Env proteins. One explanation for the absence of such an association is the diverse array of Env species present on the surface of transiently transfected cells. We also confirm that cleavage-defective mutants are antigenically different from Wt Env. These findings have implications for the use of Env binding assays as predictors of neutralizing activity, and for the development of cleavage-defective Env trimers for use as subunit immunogens.
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Herrera
authors.forename: Per Johan
authors.initials: PJ
authors.lastname: Klasse
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Michael
authors.forename: Shivani
authors.initials: S
authors.lastname: Kake
authors.forename: Kelly
authors.initials: K
authors.lastname: Barnes
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Kibler
authors.forename: Lila
authors.initials: L
authors.lastname: Campbell-Gardener
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Si
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
authors.forename: John P
authors.initials: JP
authors.lastname: Moore
authors.forename: Simon
authors.initials: S
authors.lastname: Beddows
mesh_terms: D000911:Antibodies, Monoclonal; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002462:Cell Membrane / Q000821:virology; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015483:HIV Antibodies; D015488:HIV Antigens / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D016296:Mutagenesis; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D010446:Peptide Fragments