The impact of envelope glycoprotein cleavage on the antigenicity, infectivity, and neutralization sensitivity of Env-pseudotyped human immunodeficiency virus type 1 particles.
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.
Herrera
Carolina
C
Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Room W-805, New York, NY 10021, USA.
Klasse
Per Johan
PJ
Michael
Elizabeth
E
Kake
Shivani
S
Barnes
Kelly
K
Kibler
Christopher W
CW
Campbell-Gardener
Lila
L
Si
Zhihai
Z
Sodroski
Joseph
J
Moore
John P
JP
Beddows
Simon
S
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
D000911:Antibodies, Monoclonal; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D010446:Peptide Fragments