Zika virus replication and cytopathic effects in liver cells

Kenneth E. Sherman, Susan D. Rouster, Ling X. Kong, Matthew T. Aliota, Jason T. Blackard, Gary E. Dean

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24 Scopus citations


Zika virus (ZIKV) has emerged globally as an important pathogen, since it has been recognized as a cause of microcephaly and other neurologic processes and sequalae in newborns. The virus shares homology with Hepaciviruses and therefore may be a cause of hepatitis. We sought to characterize ZIKV replication in hepatocyte-derived cell lines. Huh7.5 and HepG2 cells were infected with ZIKV and replication potential was evaluated by multiple methods including plaque assay, qRT-PCR, negative-strand ZIKV RNA production, and ZIKV NS1 protein production. Growth curves in cells and supernatant were compared to replicative capacity in Vero cells. Overall, viral replication in both hepatocyte lines approximated that observed in the Vero cells. Cell cytopathology was observed after 3 days of infection and apoptosis markers increased. Transmission electron microscopy revealed evidence of viral capsids in cells and negative staining revealed ZIKV particles in the supernatant. Conclusions: Hepatocyte-derived cell lines are permissive for ZIKV replication and produce an overt cytopathic effect consistent with development of an acute viral hepatitis. Further evaluation of replication and injury is warranted.

Original languageEnglish (US)
Article numbere0214016
JournalPloS one
Issue number3
StatePublished - Mar 2019

Bibliographical note

Funding Information:
This study was supported by a Distinguished Senior Investigator award from the University of Cincinnati College of Medicine to KES; and NIH funding grants R21AI131454, R01AI132563, R56AI132563 to MTA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2019 Sherman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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