McCrossan M, Windsor M, Ponnambalam S, Armstrong J, Wileman T
Institute for Animal Health, Pirbright Laboratories, Woking, Surrey, University of Leeds, Leeds, Yorkshire United Kingdom.
J Virol. 2001 Dec;75(23):11755-65. doi: 10.1128/JVI.75.23.11755-11765.2001.
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.
细胞分泌途径在病毒组装和包膜形成过程中很重要，并且还控制宿主蛋白的运输，如细胞因子和主要组织相容性蛋白，这些蛋白在免疫系统清除病毒的过程中发挥作用。非洲猪瘟病毒（ASFV）编码至少26种具有疏水性氨基酸片段的蛋白，提示其进入分泌途径（R. J. 亚涅斯、J. M. 罗德里格斯、M. L. 诺加尔、L. 尤斯特、C. 恩里克斯、J. F. 罗德里格斯和E. 维努埃拉，《病毒学》208:249 - 278，1995）。为了预测这些潜在膜蛋白的作用方式和位置，我们研究了感染ASFV的细胞中分泌途径的完整性。值得注意的是，ASFV导致反式高尔基体网络（TGN）标记蛋白TGN46的免疫荧光信号完全丧失，并使AP1 TGN衔接复合体分散。TGN46信号的丧失并非由于TGN46的降解，这表明TGN46重新分布到了其他膜区室。ASFV显著减缓了组织蛋白酶D向溶酶体的运输，表明TGN结构的丧失与TGN功能的丧失相关。ASFV对巨噬细胞具有嗜性，ASFV可能会损害TGN功能，以增强病毒膜蛋白的活性或抑制宿主免疫调节蛋白的功能。
