Monensin inhibits the processing of herpes simplex virus glycoproteins, their transport to the cell surface, and the egress of virions from infected cells.
HEp-2 cells or Vero cells infected with herpes simplex virus type 1 were exposed to the ionophore monensin, which is thought to block the transit of membrane vesicles from the Golgi apparatus to the cell surface. We found that yields of extracellular virus were reduced to less than 0.5% of control values by 0.2 microM monensin under conditions that permitted accumulation of cell-associated infectious virus at about 20% of control values. Viral protein synthesis was not inhibited by monensin, whereas late stages in the post-translational processing of the viral glycoproteins were blocked. The transport of viral glycoproteins to the cell surface was also blocked by monensin. Although the assembly of nucleocapsids appeared to be somewhat inhibited in monensin-treated cells, electron microscopy revealed that nucleocapsids were enveloped to yield virions, and electrophoretic analyses showed that the isolated virions contained immature forms of the envelope glycoproteins. Most of the virions which were assembled in monensin-treated cells accumulated in large intracytoplasmic vacuoles, whereas most of the virions produced by and associated with untreated cells were found attached to the cell surface. Our results implicate the Golgi apparatus in the egress of herpes simplex virus from infected cells and also suggest that complete processing of the viral envelope glycoproteins is not essential for nucleocapsid envelopment or for virion infectivity.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D005663:Furans / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D008985:Monensin / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development*; D014764:Viral Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*
D005663:Furans; D006023:Glycoproteins; D014764:Viral Proteins; D008985:Monensin