The trans Golgi network is lost from cells infected with African swine fever virus.
The cellular secretory pathway is important during the assembly and envelopment of viruses and also controls the transport of host proteins, such as cytokines and major histocompatibility proteins, that function during the elimination of viruses by the immune system. African swine fever virus (ASFV) encodes at least 26 proteins with stretches of hydrophobic amino acids suggesting entry into the secretory pathway (R. J. Yanez, J. M. Rodriguez, M. L. Nogal, L. Yuste, C. Enriquez, J. F. Rodriguez, and E. Vinuela, Virology 208:249-278, 1995). To predict how and where these potential membrane proteins function, we have studied the integrity of the secretory pathway in cells infected with ASFV. Remarkably, ASFV caused complete loss of immunofluorescence signal for the trans Golgi network (TGN) marker protein TGN46 and dispersed the AP1 TGN adapter complex. Loss of TGN46 signal was not due to degradation of TGN46, suggesting redistribution of TGN46 to other membrane compartments. ASFV markedly slowed transport of cathepsin D to lysosomes, demonstrating that loss of TGN structure correlated with loss of TGN function. ASFV shows a tropism for macrophages, and it is possible that ASFV compromises TGN function to augment the activity of viral membrane proteins or to suppress the function of host immunoregulatory proteins.
McCrossan
M
M
Institute for Animal Health, Pirbright Laboratories, Woking, Surrey, University of Leeds, Leeds, Yorkshire United Kingdom.
Windsor
M
M
Ponnambalam
S
S
Armstrong
J
J
Wileman
T
T
D033961:Adaptor Protein Complex 1; D033942:Adaptor Proteins, Vesicular Transport; D000358:African Swine Fever Virus / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins; D006056:Golgi Apparatus / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D014709:Vero Cells
D033961:Adaptor Protein Complex 1; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D002966:Clathrin; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D002402:Cathepsin D