title: African swine fever virus causes microtubule-dependent dispersal of the trans-golgi network and slows delivery of membrane protein to the plasma membrane.
abstract: Viral interference with secretory cargo is a common mechanism for pathogen immune evasion. Selective down regulation of critical immune system molecules such as major histocompatibility complex (MHC) proteins enables pathogens to mask themselves from their host. African swine fever virus (ASFV) disrupts the trans-Golgi network (TGN) by altering the localization of TGN46, an organelle marker for the distal secretory pathway. Reorganization of membrane transport components may provide a mechanism whereby ASFV can disrupt the correct secretion and/or cell surface expression of host proteins. In the study reported here, we used the tsO45 temperature-sensitive mutant of the G protein of vesicular stomatitis virus to show that ASFV significantly reduces the rate at which the protein is delivered to the plasma membrane. This is linked to a general reorganization of the secretory pathway during infection and a specific, microtubule-dependent disruption of structural components of the TGN. Golgin p230 and TGN46 are separated into distinct vesicles, whereupon TGN46 is depleted. These data suggest that disruption of the TGN by ASFV can slow membrane traffic during viral infection. This may be functionally important because infection of macrophages with virulent isolates of ASFV increased the expression of MHC class I genes, but there was no parallel increase in MHC class I molecule delivery to the plasma membrane.
authors.affiliation: Pirbright Laboratory, Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom. chris.netherton@bbsrc.ac.uk
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Netherton
authors.forename: Mari-Clare
authors.initials: MC
authors.lastname: McCrossan
authors.forename: Michael
authors.initials: M
authors.lastname: Denyer
authors.forename: Sreenivasan
authors.initials: S
authors.lastname: Ponnambalam
authors.forename: John
authors.initials: J
authors.lastname: Armstrong
authors.forename: Haru-Hisa
authors.initials: HH
authors.lastname: Takamatsu
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wileman
mesh_terms: D000358:African Swine Fever Virus / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D008565:Membrane Proteins / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology / Q000821:virology*; D014709:Vero Cells; D021601:trans-Golgi Network / Q000648:ultrastructure / Q000821:virology*
chemical_list: D008565:Membrane Proteins