Syncytia formation induced by coronavirus infection is associated with fragmentation and rearrangement of the Golgi apparatus.
Coronavirus mouse hepatitis virus (MHV) possesses a membrane glycoprotein (M) which is targeted to the Golgi apparatus (GA). We used immunocytochemistry with an organelle-specific antiserum to investigate the morphologic changes of the GA during infection of L2 murine fibroblasts with MHV-A59. Twenty-four hours after infection the GA was fragmented and translocated in the center of syncytia, while the microtubular network was also rearranged displaying radiating elements toward the center of syncytia. Two fusion-defective mutants, which contain an identical amino acid substitution in the cleavage signal sequence of the spike glycoprotein (S), induced fragmentation of the GA. However, the GA migrated only partially to the centers of syncytia during infection with these mutants. Revertant viruses, in which the above mutation was corrected, had fusion properties and GA staining similar to wtMHV-A59. Experiments with brefeldin A (BFA), which induces redistribution of the GA into the rough endoplasmic reticulum (RER), revealed that an intact GA for a period of 4-16 hr postinfection, is required for coronavirus replication and syncytia formation. Thus, during MHV infection, syncytia formation is associated with fragmentation of the GA, followed by a previously undescribed phenomenon of migration of the organelle into the centers of syncytia. The fragmentation of the GA, however, may occur without the formation of syncytia. Therefore, two distinct mechanisms may be responsible for the fragmentation of the GA and its subsequent migration to the center of syncytia.
Lavi
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E
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-6079, USA. ehud_lavi.ap@pat1a.med.upenn.edu
Wang
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Q
Weiss
S R
SR
Gonatas
N K
NK
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D020126:Brefeldin A; D002460:Cell Line; D003517:Cyclopentanes / Q000494:pharmacology; D003673:Defective Viruses / Q000502:physiology; D018870:Endoplasmic Reticulum, Rough / Q000648:ultrastructure / Q000821:virology; D015726:Giant Cells / Q000648:ultrastructure / Q000821:virology*; D006056:Golgi Apparatus / Q000648:ultrastructure / Q000821:virology*; D051379:Mice; D008870:Microtubules / Q000648:ultrastructure / Q000821:virology; D006517:Murine hepatitis virus / Q000187:drug effects / Q000502:physiology*; D009154:Mutation
D000998:Antiviral Agents; D003517:Cyclopentanes; D020126:Brefeldin A