Blocking Zika virus vertical transmission View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Pinar Mesci, Angela Macia, Spencer M. Moore, Sergey A. Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R. Fernandes, Nicole A. Suarez, Matthew J. Kolar, Sandro Montefusco, Scott C. Rosenberg, Roberto H. Herai, Fernanda R. Cugola, Fabiele B. Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D. Momper, Jair L. Siqueira-Neto, Kevin D. Corbett, Patricia C. B. Beltrão-Braga, Alexey V. Terskikh, Alysson R. Muotri

ABSTRACT

The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity. More... »

PAGES

1218

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-19526-4

    DOI

    http://dx.doi.org/10.1038/s41598-018-19526-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1100406273

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29352135


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