Zika, dengue and yellow fever viruses induce differential anti-viral immune responses in human monocytic and first trimester trophoblast cells

Huanle Luo, Evandro R. Winkelmann, Ildefonso Fernandez-Salas, Li Li, Sandra V. Mayer, Rogelio Danis-Lozano, Rosa Ma Sanchez-Casas, Nikos Vasilakis, Robert Tesh, Alan Barrett, Scott Weaver, Tian Wang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neonatal birth defects, but the causative mechanism is incompletely understood. ZIKV shares sequence homology and early clinical manifestations with yellow fever virus (YFV) and dengue virus (DENV) and are all transmitted in urban cycles by the same species of mosquitoes. However, YFV and DENV have been rarely reported to cause congenital diseases. Here, we compared infection with a contemporary ZIKV strain (FSS13025) to YFV17D and DENV-4 in human monocytic cells (THP-1) and first-trimester trophoblasts (HTR-8). Our results suggest that all three viruses have similar tropisms for both cells. Nevertheless, ZIKV induced strong type 1 IFN and inflammatory cytokine and chemokine production in monocytes and peripheral blood mononuclear cells. Furthermore, ZIKV infection in trophoblasts induced lower IFN and higher inflammatory immune responses. Placental inflammation is known to contribute to the risk of brain damage in preterm newborns. Inhibition of toll-like receptor (TLR)3 and TLR8 each abrogated the inflammatory cytokine responses in ZIKV-infected trophoblasts. Our findings identify a potential link between maternal immune activation and ZIKV-induced congenital diseases, and a potential therapeutic strategy that targets TLR-mediated inflammatory responses in the placenta.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalAntiviral Research
Volume151
DOIs
StatePublished - Mar 1 2018

Fingerprint

Yellow fever virus
Dengue
Trophoblasts
First Pregnancy Trimester
Dengue Virus
Culicidae
Toll-Like Receptor 3
Cytokines
Flavivirus
Tropism
Toll-Like Receptors
Sequence Homology
Chemokines
Placenta
Zika Virus Infection
Zika Virus
Monocytes
Blood Cells
Mothers
Viruses

Keywords

  • Flavivirus
  • Immunity
  • Trophoblast
  • Zika virus

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Zika, dengue and yellow fever viruses induce differential anti-viral immune responses in human monocytic and first trimester trophoblast cells. / Luo, Huanle; Winkelmann, Evandro R.; Fernandez-Salas, Ildefonso; Li, Li; Mayer, Sandra V.; Danis-Lozano, Rogelio; Sanchez-Casas, Rosa Ma; Vasilakis, Nikos; Tesh, Robert; Barrett, Alan; Weaver, Scott; Wang, Tian.

In: Antiviral Research, Vol. 151, 01.03.2018, p. 55-62.

Research output: Contribution to journalArticle

Luo, Huanle ; Winkelmann, Evandro R. ; Fernandez-Salas, Ildefonso ; Li, Li ; Mayer, Sandra V. ; Danis-Lozano, Rogelio ; Sanchez-Casas, Rosa Ma ; Vasilakis, Nikos ; Tesh, Robert ; Barrett, Alan ; Weaver, Scott ; Wang, Tian. / Zika, dengue and yellow fever viruses induce differential anti-viral immune responses in human monocytic and first trimester trophoblast cells. In: Antiviral Research. 2018 ; Vol. 151. pp. 55-62.
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