Differential effect of monensin on enveloped viruses that form at distinct plasma membrane domains.
We have observed a striking differential effect of the ionophore, monensin, on replication of influenza virus and vesicular stomatitis virus (VSV) in Madin-Darby canine kidney (MDCK) and baby hamster kidney (BHK21) cells. In MDCK cells, influenza virus is assembled at the apical surfaces, whereas VSV particles bud from the basolateral membranes; no such polarity of maturation is exhibited in BHK21 cells. A 10(-6) M concentration of monensin reduces VSV yields in MDCK cells by greater than 90% as compared with controls, whereas influenza virus yields are unaffected. In BHK21 cells, monensin also inhibits VSV production, but influenza virus is also sensitive to the ionophore. Immunofluorescent staining of fixed and unfixed MDCK monolayers indicates that VSV glycoproteins are synthesized in the presence of monensin, but their appearance on the plasma membrane is blocked. Electron micrographs of VSV-infected MDCK cells treated with monensin show VSV particles aggregated within dilated cytoplasmic vesicles. Monensin-treated influenza virus-infected MDCK cells also contain dilated cytoplasmic vesicles, but virus particles were not found in these structures, and numerous influenza virions were observed budding at the cell surface. These results indicate that influenza virus glycoprotein transport is not blocked by monensin treatment, whereas there is a block in transport of VSV G protein. Thus it appears that at least two distinct pathways of transport of glycoproteins to the plasma membrane exist in MDCK cells, and only one of them is blocked by monensin.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000382:microbiology*; D006224:Cricetinae; D004285:Dogs; D005663:Furans / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism; D009980:Influenza A virus / Q000187:drug effects*; D008985:Monensin / Q000494:pharmacology*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D005663:Furans; D006023:Glycoproteins; D014764:Viral Proteins; D008985:Monensin