Frontiers in Cellular and Infection Microbiology (Jul 2020)

Senescence in Monocytes Facilitates Dengue Virus Infection by Increasing Infectivity

  • Tzu-Han Hsieh,
  • Tsung-Ting Tsai,
  • Chia-Ling Chen,
  • Ting-Jing Shen,
  • Ting-Jing Shen,
  • Ming-Kai Jhan,
  • Ming-Kai Jhan,
  • Po-Chun Tseng,
  • Po-Chun Tseng,
  • Chiou-Feng Lin,
  • Chiou-Feng Lin,
  • Chiou-Feng Lin,
  • Chiou-Feng Lin

DOI
https://doi.org/10.3389/fcimb.2020.00375
Journal volume & issue
Vol. 10

Abstract

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Aging and chronic condition increase the incidence of dengue virus (DENV) infection, generally through a mechanism involving immunosenescence; however, the alternative effects of cellular senescence, which alters cell susceptibility to viral infection, remain unknown. Human monocytic THP-1 cells (ATCC TIB-202) treated with D-galactose to induce cellular senescence were susceptible to DENV infection. These senescent cells showed increased viral entry/binding, gene/protein expression, and dsRNA replication. The use of a replicon system showed that pharmacologically induced senescence did not enhance the effects on viral protein translation. By examining viral receptor expression, we found increased expression of CD209 (DC-SIGN) in the senescent cells. Interleukin (IL)-10 was aberrantly produced at high levels by the senescent cells, and the expression of the DENV receptor DC-SIGN was increased in these senescent cells, partially via IL-10-mediated regulation of the JAK2-STAT3 signaling pathway. The results demonstrate that a senescent phenotype facilitates DENV infection, probably by increasing DC-SIGN expression.

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