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Am J Reprod Immunol. 2016 Nov;76(5):348-357. doi: 10.1111/aji.12578. Epub 2016 Sep 10.

HSV-2 enhances ZIKV infection of the placenta and induces apoptosis in first-trimester trophoblast cells.

Author information

1
Division of Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
2
Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
3
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
4
Division of Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. gil.mor@yale.edu.

Abstract

PROBLEM:

Zika virus (ZIKV) has gained public concern for its association with microcephaly in infants born to ZIKV-infected mothers. To reach the fetus the virus must overcome the defense mechanisms provided by trophoblast cells. Additionally, in the first trimester, the integrity of the placenta is critical for fetal protection as damage to differentiating trophoblast can affect placental formation and function. We sought to investigate the effect of ZIKV infection on trophoblast cells and the factors that might increase the risk for ZIKV infection during pregnancy.

METHODS:

First-trimester human trophoblast cells, Swan 7.1, were infected with ZIKV, herpes simplex virus-2 (HSV-2), and yellow fiver (YFV). C57BL/6 pregnant mice were infected with HSV-2, ZIKV, or coinfection. Placental viral titers were determined by RT-PCR.

RESULTS:

ZIKV infection induces apoptosis in first-trimester trophoblasts and prevents differentiation of these cells. Furthermore, HSV-2 infection enhances placental sensitivity to ZIKV by enhancing the expression of TAM receptors, which facilitate ZIKV cell entry.

CONCLUSION:

These findings may explain the mechanism by which ZIKV breaches the placental barrier to access the fetus. Furthermore, our results suggest that patients with HSV-2 infection are at a higher risk for the teratogenic effects induced by ZIKV.

KEYWORDS:

HSV-1/2; co-infection; fetal viral infection; pika virus; placenta; pregnancy

Comment in

PMID:
27613665
DOI:
10.1111/aji.12578
[Indexed for MEDLINE]

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