Effect of monensin on the assembly of Uukuniemi virus in the Golgi complex.
The effect of the carboxylic ionophore monensin on the maturation of Uukuniemi virus, a bunyavirus, and the transport of its two membrane glycoproteins, G1 and G2, were studied in chicken embryo fibroblasts and baby hamster kidney cells. Virus maturation, which occurs in the Golgi complex (E. Kuismanen, K. Hedman, J. Saraste, and R. F. Pettersson, Mol. Cell. Biol. 2:1444-1458, 1982; E. Kuismanen, B. Bång, M. Hurme, and R. F. Pettersson, J. Virol. 51:137-146, 1984), was effectively inhibited by the drug (1 or 10 microM) as studied by electron microscopy and by assaying the release of infectious or radiolabeled virus. Immunoelectron microscopy showed that association of viral nucleocapsids with the cytoplasmic surface of glycoprotein-containing Golgi membranes, a prerequisite for virus budding, was unaffected by monensin. In the presence of the drug, the virus glycoproteins assembled into long, tubular structures extending into the lumen of Golgi-derived vacuoles, suggesting that monensin inhibited a terminal step in the assembly of the virus. Intracellular transport and expression of the virus membrane glycoproteins G1 and G2 at the cell surface were not inhibited by monensin as studied by immunocytochemical and radiolabeling techniques. Pulse-chase experiments in the presence of monensin showed that intracellular G1 acquired only partially endo-H-resistant glycans. The sialylation of G1 appearing on the cell surface in the presence of the drug was decreased, whereas sialylation of G2 apparently was inhibited to a lesser extent, as shown by external labeling of the cells with the periodate-boro[3H]hydride method. Thus, monensin exerted a differential effect on the terminal glycosylation of G1 and G2. Unlike several membrane and secretory glycoproteins, both G1 and G2 could enter a functional transport pathway in the presence of monensin and become expressed at the cell surface.
D000818:Animals; D002043:Bunyaviridae / Q000187:drug effects*; D002478:Cells, Cultured; D002645:Chickens; D006224:Cricetinae; D005663:Furans / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000382:microbiology*; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology*; D009024:Morphogenesis / Q000187:drug effects; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D005663:Furans; D008565:Membrane Proteins; D014764:Viral Proteins; D008985:Monensin