Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
Effects of brefeldin A on the processing of viral envelope glycoproteins in murine erythroleukemia cells.
J Biol Chem. 1991 May 15;266(14):9173-9. Unique Identifier : AIDSLINE MED/91225024 Ulmer JB; Palade GE; Department of Cell Biology, Yale University School of Medicine,; New Haven, Connecticut 06510.
Abstract:
This paper documents the effects of brefeldin A (BFA) on the processing and transport of viral envelope glycoproteins in a retrovirus-transformed murine erythroleukemia (MEL) cell line. BFA is a fungal metabolite that disrupts intracellular membrane traffic at the endoplasmic reticulum (ER)-Golgi complex junction. In MEL cells, BFA inhibited the processing of the newly synthesized precursor, gPr90env, of the murine leukemia virus envelope protein, gp70, and curtailed the budding of virions into the culture medium by blocking the transport of this protein out of the ER. The block resulted in the intracellular accumulation of gPr90env and two putative products of its processing (78 and 66 kDa). The results of endoglycosidase (endo) H and D digestion of the viral glycoproteins in the presence and absence of BFA indicated that (i) there was no glycoprotein processing during the first approximately 2 h of the BFA block; (ii) active Golgi enzymes relocated to the ER in approximately 2 h during BFA treatment, resulting in the production of partially endo H-resistant forms of the spleen focus-forming virus glycoprotein, gp55 (in controls, this glycoprotein was generally retained in the ER as an endo H-sensitive entity); and (iii) proteolytic processing of gPr90env to gp70 occurred prior to the acquisition of endo H resistance and at approximately the same time as endo D sensitivity (i.e. in a cis Golgi compartment). In control cells, the spleen focus-forming virus glycoprotein, gp55, underwent turnover with a half-life of approximately 5 h. In contrast, its turnover was considerably slower during BFA treatment (t 1/2 = approximately 20 h), suggesting that transport of gp55 out of the ER was required for its degradation or that BFA afforded it protection from proteolysis within the ER.
Keywords: Animal Biological Transport/DRUG EFFECTS Cell Compartmentation Cyclopentanes/*PHARMACOLOGY Endoplasmic Reticulum/METABOLISM Gene Products, env/*METABOLISM Glycosylation Golgi Apparatus/METABOLISM In Vitro Leukemia Viruses, Murine/*METABOLISM Leukemia, Erythroblastic, Acute Mice Molecular Weight Protein Processing, Post-Translational/*DRUG EFFECTS Spleen Focus-Forming Viruses/*METABOLISM Support, U.S. Gov't, P.H.S. Tumor Cells, Cultured Viral Envelope Proteins/*METABOLISM JOURNAL ARTICLE
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
