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Vulnerability of primitive human placental trophoblast to Zika virus.

Publication ,  Journal Article
Sheridan, MA; Yunusov, D; Balaraman, V; Alexenko, AP; Yabe, S; Verjovski-Almeida, S; Schust, DJ; Franz, AW; Sadovsky, Y; Ezashi, T; Roberts, RM
Published in: Proc Natl Acad Sci U S A
February 28, 2017

Infection of pregnant women by Asian lineage strains of Zika virus (ZIKV) has been linked to brain abnormalities in their infants, yet it is uncertain when during pregnancy the human conceptus is most vulnerable to the virus. We have examined two models to study susceptibility of human placental trophoblast to ZIKV: cytotrophoblast and syncytiotrophoblast derived from placental villi at term and colonies of trophoblast differentiated from embryonic stem cells (ESC). The latter appear to be analogous to the primitive placenta formed during implantation. The cells from term placentas, which resist infection, do not express genes encoding most attachment factors implicated in ZIKV entry but do express many genes associated with antiviral defense. By contrast, the ESC-derived trophoblasts possess a wide range of attachment factors for ZIKV entry and lack components of a robust antiviral response system. These cells, particularly areas of syncytiotrophoblast within the colonies, quickly become infected, produce infectious virus and undergo lysis within 48 h after exposure to low titers (multiplicity of infection > 0.07) of an African lineage strain (MR766 Uganda: ZIKVU) considered to be benign with regards to effects on fetal development. Unexpectedly, lytic effects required significantly higher titers of the presumed more virulent FSS13025 Cambodia (ZIKVC). Our data suggest that the developing fetus might be most vulnerable to ZIKV early in the first trimester before a protective zone of mature villous trophoblast has been established. Additionally, MR766 is highly trophic toward primitive trophoblast, which may put the early conceptus of an infected mother at high risk for destruction.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 28, 2017

Volume

114

Issue

9

Start / End Page

E1587 / E1596

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Uganda
  • Trophoblasts
  • Pregnancy Trimester, First
  • Pregnancy
  • Placenta
  • Humans
  • Female
  • Embryonic Stem Cells
 

Citation

APA
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MLA
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Sheridan, M. A., Yunusov, D., Balaraman, V., Alexenko, A. P., Yabe, S., Verjovski-Almeida, S., … Roberts, R. M. (2017). Vulnerability of primitive human placental trophoblast to Zika virus. Proc Natl Acad Sci U S A, 114(9), E1587–E1596. https://doi.org/10.1073/pnas.1616097114
Sheridan, Megan A., Dinar Yunusov, Velmurugan Balaraman, Andrei P. Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J. Schust, et al. “Vulnerability of primitive human placental trophoblast to Zika virus.Proc Natl Acad Sci U S A 114, no. 9 (February 28, 2017): E1587–96. https://doi.org/10.1073/pnas.1616097114.
Sheridan MA, Yunusov D, Balaraman V, Alexenko AP, Yabe S, Verjovski-Almeida S, et al. Vulnerability of primitive human placental trophoblast to Zika virus. Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):E1587–96.
Sheridan, Megan A., et al. “Vulnerability of primitive human placental trophoblast to Zika virus.Proc Natl Acad Sci U S A, vol. 114, no. 9, Feb. 2017, pp. E1587–96. Pubmed, doi:10.1073/pnas.1616097114.
Sheridan MA, Yunusov D, Balaraman V, Alexenko AP, Yabe S, Verjovski-Almeida S, Schust DJ, Franz AW, Sadovsky Y, Ezashi T, Roberts RM. Vulnerability of primitive human placental trophoblast to Zika virus. Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):E1587–E1596.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 28, 2017

Volume

114

Issue

9

Start / End Page

E1587 / E1596

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Uganda
  • Trophoblasts
  • Pregnancy Trimester, First
  • Pregnancy
  • Placenta
  • Humans
  • Female
  • Embryonic Stem Cells