Effects of signal peptide exchange on HIV-1 glycoprotein expression and viral infectivity in mammalian cells

• Published in: FEBS letters Vol. 580; no. 15; pp. 3775 - 3778
• Main Authors: Pfeiffer, Tanya, Pisch, Thorsten, Devitt, Gerard, Holtkotte, Denise, Bosch, Valerie
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 26.06.2006
• Subjects: Cell Line; Gene Expression Regulation, Viral; Glycoproteins - genetics; Glycoproteins - metabolism; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - metabolism; HIV glycoprotein incorporation; HIV glycoprotein transport; HIV signal peptide; HIV-1 - genetics; HIV-1 - pathogenicity; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Membrane Fusion; Molecular Sequence Data; Protein Sorting Signals - physiology; Virion - metabolism; HIV glycoprotein transport; HIV signal peptide; HIV glycoprotein incorporation
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.05.070

In certain cell systems, exchange of the human immunodeficiency virus (HIV) Env signal peptide (SP) sequence with that of heterologous SPs has been shown to increase gp120 transport and secretion. Here we demonstrate that exchange of the HIV-Env-SP with those from erythropoietin or tissue plasminogen activator in the proviral context does not increase wild-type membrane-bound Env expression or incorporation into released virions. In fact, virion infectivities were decreased. These infectivity decreases were largely due to effects on Env transport and/or function and only to a minor extent to cis effects as a result of the sequence exchanges themselves. Thus, in fact, it is not advantageous to employ heterologous SPs to achieve high-level expression of functional cell surface membrane- or virion-associated HIV-Env.