Foot-and-mouth disease virus 3C protease induces fragmentation of the Golgi compartment and blocks intra-Golgi transport.

Abstract

Picornavirus infection can cause Golgi fragmentation and impose a block in the secretory pathway which reduces expression of major histocompatibility antigens at the plasma membrane and slows secretion of proinflammatory cytokines. In this study, we show that Golgi fragmentation and a block in secretion are induced by expression of foot-and-mouth disease virus (FMDV) 3C(pro) and that this requires the protease activity of 3C(pro). 3C(pro) caused fragmentation of early, medial, and late Golgi compartments, but the most marked effect was on early Golgi compartments, indicated by redistribution of ERGIC53 and membrin. Golgi fragments were dispersed in the cytoplasm and were able to receive a model membrane protein exported from the endoplasmic reticulum (ER). Golgi fragments were, however, unable to transfer the protein to the plasma membrane, indicating a block in intra-Golgi transport. Golgi fragmentation was coincident with a loss of microtubule organization resulting from an inhibition of microtubule regrowth from the centrosome. Inhibition of microtubule regrowth also required 3C(pro) protease activity. The loss of microtubule organization induced by 3C(pro) caused Golgi fragmentation, but loss of microtubule organization does not block intra-Golgi transport. It is likely that the block of intra-Golgi transport is imposed by separate actions of 3C(pro), possibly through degradation of proteins required for intra-Golgi transport.

• Authors: Zhigang Zhou, Mette M Mogensen, Penny P Powell, Stephen Curry, Thomas Wileman
• Journal: Journal of virology (J Virol) Vol. 87 Issue 21 Pg. 11721-9 (Nov 2013) ISSN: 1098-5514 [Electronic] United States
• PMID: 23986596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Viral Proteins
• Cysteine Endopeptidases
• 3C Viral Proteases
• 3C proteases

Topics

• 3C Viral Proteases
• Animals
• Chlorocebus aethiops
• Cysteine Endopeptidases (metabolism)
• Foot-and-Mouth Disease Virus (pathogenicity)
• Golgi Apparatus (metabolism, physiology, ultrastructure)
• Host-Pathogen Interactions
• Microscopy, Fluorescence
• Microtubules (metabolism, ultrastructure)
• Protein Transport
• Vero Cells
• Viral Proteins (metabolism)