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Journal of Virology, June 2001, p. 5263-5276, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5263-5276.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of Two Sequences in the Cytoplasmic Tail of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein That Inhibit Cell Surface Expression

Andreas Bültmann,1 Walter Muranyi,1 Brian Seed,2 and Jürgen Haas1,*

Max von Pettenkofer-Institut, Genzentrum, Ludwig Maximilians Universität München, Munich, Germany,1 and Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 021142

Received 28 April 2000/Accepted 3 March 2001

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. In accordance with the results in heterologous systems, an internal deletion of both elements considerably increased surface expression of gp160.

* Corresponding author. Mailing address: Max von Pettenkofer-Institut, Genzentrum, LMU München, Feodor-Lynen-Str. 25, 81377 Munich, Germany. Phone: 49 89 2180 6852. Fax: 49 89 2180 6899. E-mail: haas{at}lmb.uni-muenchen.de.

Journal of Virology, June 2001, p. 5263-5276, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5263-5276.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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