title: Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing.
abstract: Intracellular transport and processing of the human immunodeficiency virus type 1 (HIV-1) envelope precursor polyprotein, gp160, proceeds via the endoplasmic reticulum (ER) and Golgi complex. We examined gp160 processing during the production of HIV-1 virions in transfected HeLa cells using wild-type and env mutant proviral molecular clones. Results from pulse-chase analyses indicated that a single amino acid substitution within a highly conserved domain of the env gene impaired gp160 export from the ER, leading to an increase in oligomeric forms of gp160 and a decrease in gp120 production. In contrast, gp160 which contained a mutated cleavage site was able to traverse the ER/Golgi complex, even in the absence of proteolytic processing, and become incorporated into budding virions. These findings indicate that export from the ER is a point in the intracellular trafficking of gp160 that is crucial to the production of the mature envelope components.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: R L
authors.initials: RL
authors.lastname: Willey
authors.forename: T
authors.initials: T
authors.lastname: Klimkait
authors.forename: D M
authors.initials: DM
authors.lastname: Frucht
authors.forename: J S
authors.initials: JS
authors.lastname: Bonifacino
authors.forename: M A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D006026:Glycoside Hydrolases; D006056:Golgi Apparatus / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D015345:Oligonucleotide Probes; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D011499:Protein Processing, Post-Translational; D014162:Transfection; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D014771:Virion / Q000235:genetics
chemical_list: D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D011498:Protein Precursors; D014759:Viral Envelope Proteins; D006026:Glycoside Hydrolases