Viral binding-induced signaling drives a unique and extended intracellular trafficking pattern during infection of primary monocytes

Jung Heon Kim, Collins Mcmillen Donna, Patrizia Caposio, Andrew D. Yurochko

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 ignaling 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.

Original languageEnglish (US)
Pages (from-to)8819-8824
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number31
DOIs
StatePublished - Aug 2 2016

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Cytomegalovirus
Monocytes
Endosomes
trans-Golgi Network
Infection
Integrins
Viral DNA
Virus Diseases
Endothelial Cells
Fibroblasts
Survival
DNA

ASJC Scopus subject areas

  • General

Cite this

Viral binding-induced signaling drives a unique and extended intracellular trafficking pattern during infection of primary monocytes. / Kim, Jung Heon; Donna, Collins Mcmillen; Caposio, Patrizia; Yurochko, Andrew D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 31, 02.08.2016, p. 8819-8824.

Research output: Contribution to journalArticle

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