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  • 标题:Viral binding-induced signaling drives a unique and extended intracellular trafficking pattern during infection of primary monocytes
  • 作者:Jung Heon Kim ; Donna Collins-McMillen ; Patrizia Caposio
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2016
  • 卷号:113
  • 期号:31
  • 页码:8819-8824
  • DOI:10.1073/pnas.1604317113
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:We initiated experiments to examine the infection of monocytes postentry. New data show that human cytomegalovirus (HCMV) DNA is detected in the nucleus beginning only at 3 d postinfection in monocytes, compared with 30 min postinfection in fibroblasts and endothelial cells, suggesting that HCMV nuclear translocation in monocytes is distinct from that seen in other cell types. We now show that HCMV is initially retained in early endosomes and then moves sequentially to the trans-Golgi network (TGN) and recycling endosomes before nuclear translocation. HCMV is retained initially as a mature particle before deenvelopment in recycling endosomes. Disruption of the TGN significantly reduced nuclear translocation of viral DNA, and HCMV nuclear translocation in infected monocytes was observed only when correct gH/gL/UL128-131/integrin/c-Src signaling occurred. Taken together, our findings show that viral binding of the gH/gL/UL128-131 complex to integrins and the ensuing c-Src signaling drive a unique nuclear translocation pattern that promotes productive infection and avoids viral degradation, suggesting that it represents an additional viral evasion/survival strategy.
  • 关键词:monocytes ; viral trafficking ; gH/gL/UL128-131 complex ; integrins ; nuclear translocation pathway
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