Identification of two sequences in the cytoplasmic tail of the human immunodeficiency virus type 1 envelope glycoprotein that inhibit cell surface expression

Journal of Virology
A BültmannJ Haas

Abstract

During synthesis and export of protein, the majority of the human immunodeficiency virus type 1 (HIV-1) Env glycoprotein gp160 is retained in the endoplasmic reticulum (ER) and subsequently ubiquitinated and degraded by proteasomes. Only a small fraction of gp160 appears to be correctly folded and processed and is transported to the cell surface, which makes it difficult to identify negative sequence elements regulating steady-state surface expression of Env at the post-ER level. Moreover, poorly localized mRNA retention sequences inhibiting the nucleocytoplasmic transport of viral transcripts interfere with the identification of these sequence elements. Using two heterologous systems with CD4 or immunoglobulin extracellular/transmembrane domains in combination with the gp160 cytoplasmic domain, we were able to identify two membrane-distal, neighboring motifs, is1 (amino acids 750 to 763) and is2 (amino acids 764 to 785), which inhibited surface expression and induced Golgi localization of the chimeric proteins. To prove that these two elements act similarly in the homologous context of the Env glycoprotein, we generated a synthetic gp160 gene with synonymous codons, the transcripts of which are not retained within the nucleus....Continue Reading

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Citations

Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jian YanDavid B Weiner
Jul 20, 2006·DNA and Cell Biology·Sanjeev KumarDavid B Weiner
Feb 26, 2010·Journal of Virology·Elena SokolskajaJeremy Luban
May 28, 2013·Retrovirology·Eveline Santos da SilvaDanielle Perez Bercoff
Jun 24, 2008·Critical Reviews in Biochemistry and Molecular Biology·Judith M WhiteKathryn Schornberg
Jul 19, 2011·Journal of Molecular Biology·Mary Ann CheckleyEric O Freed
Aug 6, 2011·Peptides·Joaquim Xavier da SilvaEnrique Roberto Argañaraz
Nov 14, 2014·PLoS Pathogens·Elisabetta GroppelliClare Jolly
Apr 6, 2018·Journal of Virology·Luis R Castillo-MenendezJoseph Sodroski
Feb 20, 2018·Virology Journal·Cyprien BeraudDanielle Perez Bercoff

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