African Swine Fever Virus Causes Microtubule-Dependent Dispersal of the trans -Golgi Network and Slows Delivery of Membrane Protein to the PlasmaMembrane

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.

Redistribution of Endosomal Membranes to the African Swine Fever Virus Replication Site

“…Immunofluorescence analysis shows areas of apparent exclusion of resident ER proteins relative to the rest of the cytoplasm [21,34] where endosomal membranes are accumulated. However, both ER and endosomal membranes could be coincident at the inner part of the VFs in direct contact of areas of viral morphogenesis, which seems possible, but should be considered for further studies.…”

African Swine Fever Virus

“…The cellular microtubule network becomes disorganized after the onset of viral DNA replication and formation of virus factories, likely resulting from redistribution of centrosome proteins and functional disruption of centrosomes, which lose the ability to nucleate microtubules (Jouvenet and Wileman 2005). Microtubule-dependent disruption of the TGN is linked to the ability of ASFV to slow protein traffic to the plasma membrane, a potential mechanism for evading the immune system (Netherton et al 2006). ASFV infection also increased the formation of a stable, acylated subpopulation of microtubules in infected cells (Jouvenet et al 2004).…”

Inhibition of the Secretory Pathway by Foot-and-Mouth Disease Virus 2BC Protein Is Reproduced by Coexpression of 2B with 2C, and the Site of Inhibition Is Determined by the Subcellular Location of 2C

“…This strategy is not limited to picornaviruses. Recent work shows that the secretory pathway is compromised in cells infected with African swine fever virus (19) and in cells expressing the nonstructural proteins of hepatitis C virus (15), and in common with FMDV, both viruses cause persistent infections and have proved difficult to control through vaccination.…”