Effects of signal peptide exchange on HIV-1 glycoprotein expression and viral infectivity in mammalian cells.
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 infectivity was 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.
Pfeiffer
Tanya
T
Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Pisch
Thorsten
T
Devitt
Gerard
G
Holtkotte
Denise
D
Bosch
Valerie
V
D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000502:physiology*; D014771:Virion / Q000378:metabolism
D006023:Glycoproteins; D015699:HIV Envelope Protein gp120; D021382:Protein Sorting Signals