Congenital Zika virus, like rubella virus, infects fetal cortical progenitor cells.

Many viral infections, especially rubella, can affect the developing nervous system. Perhaps one way in which they do so is to cross the placenta from the infected mother to the infant, where they damage the developing cortical layers of the fetal brain's cerebrum. The following recent studies support this hypothesis.

ABSTRACT

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Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome

Mihaela Lazar, Ludmila Perelygina, Roosecelis Martines, Patricia Greer, Christopher D. Paddock, Gheorghe Peltecu, Emilia Lupulescu, Joseph Icenogle, and Sherif R. Zakib

An estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants.

Methods

Cells and organs involved in RV replication were identified in paraffin-embedded autopsy tissues from three fatal case-patients by histopathologic examination and immunohistochemical (IHC) staining using a rabbit polyclonal RV antibody. Normal rabbit antisera and RV antisera preabsorbed with highly purified RV served as negative controls.

Results

RV antigen was found in interstitial fibroblasts in the heart, adventitial fibroblasts of large blood vessels, alveolar macrophages, progenitor cells of the outer granular layer of the brain, and in capillary endothelium and basal plate in the placenta. The antibody specificity was verified by IHC staining of multiple tissue sections from other infectious disease cases. RV infection of each cell type is consistent with abnormalities which have been identified in patients with CRS, in the heart, large blood vessels, and brain. Antigen distribution was consistent with inflammatory response to vascular injury and systemic spread of RV.

Conclusions

The identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS.


ABSTRACT

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Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth

Hengli Tang11correspondenceemail, Christy Hammack11, Sarah C. Ogden11, Zhexing Wen11, Xuyu Qian11, Yujing Li, Bing Yao, Jaehoon Shin, Feiran Zhang, Emily M. Lee, Kimberly M. Christian, Ruth A. Didier, Peng Jin, Hongjun Songcorrespondenceemail, Guo-li Ming

Publication stage: In Press Corrected Proof

DOI: http://dx.doi.org/10.1016/j.stem.2016.02.016

Summary

The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.

Received: February 24, 2016; Received in revised form: February 28, 2016; Accepted: February 29, 2016; Published: March 4, 2016

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