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Journal of Virology, November 2006, p. 11385-11392, Vol. 80, No. 22
0022-538X/06/$08.00+0 doi:10.1128/JVI.00439-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Department of Immunology, Pirbright Laboratory, Institute for Animal Health, Ash Road, Woking GU24 0NF,1 Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT,2 Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer BN1 9QG, United Kingdom3
Received 2 March 2006/ Accepted 28 August 2006
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.
Published
ahead of print on 6 September 2006.
¶ Present address: Laboratory for Clinical and Molecular Virology, University of Edinburgh, Summerhall, Edinburgh, Scotland EH9 1QH, United Kingdom.
Present
address: Infection and Immunity, School of Medicine, Health Policy and
Practice, Institute of Health, University of East Anglia, Norwich NR4
TJU, United Kingdom.
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