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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Vulnerability of primitive human placental trophoblast to Zika virus

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Sheridan, Megan A. ; Yunusov, Dinar ; Balaraman, Velmurugan ; Alexenko, Andrei P. ; Yabe, Shinichiro ; Verjovski-Almeida, Sergio ; Schust, Danny J. ; Franz, Alexander W. ; Sadovsky, Yoel ; Toshihiko, Ezashi ; Roberts, R. Michael
Total Authors: 11
Document type: Journal article
Source: Proceedings of the National Academy of Sciences of the United States of America; v. 114, n. 9, p. E1587-E1596, FEB 28 2017.
Web of Science Citations: 44

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 lowtiters (multiplicity of infection > 0.07) of an African lineage strain (MR766 Uganda: ZIKV(U)) considered to be benignwith regards to effects on fetal development. Unexpectedly, lytic effects required significantly higher titers of the presumed more virulent FSS13025 Cambodia (ZIKV(C)). 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. (AU)

FAPESP's process: 14/03620-2 - Characterization of the mechanisms of action of long non-coding RNAs involved with gene activation programs in human cells
Grantee:Sergio Verjovski Almeida
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/51152-7 - Functional characterization of long non-coding RNA transcribed from the antisense strand in the VEGFA gene locus
Grantee:Dinar Yunusov
Support type: Scholarships in Brazil - Doctorate (Direct)