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Sci Rep. 2018 Jan 19;8(1):1218. doi: 10.1038/s41598-018-19526-4.

Blocking Zika virus vertical transmission.

Author information

1
University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, La Jolla, CA, 92037-0695, USA.
2
Sanford Burnham Prebys Medical Discovery Institute, 10901N. Torrey Pines Rd., La Jolla, CA, 92037, USA.
3
Salk Institute for Biological Studies, Clayton Foundation Laboratories for Peptide Biology, Helmsley Center for Genomic Medicine, La Jolla, California, USA.
4
University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, Center for Discovery and Innovation in Parasitic Diseases, 9500 Gilman Dr., La Jolla, CA, 92093, MC 0755, USA.
5
Ludwig Institute for Cancer Research, San Diego Branch, 9500 Gilman Dr., La Jolla, CA, 92093, MC 2385, USA.
6
University of California San Diego, Department of Cellular and Molecular Medicine, 9500 Gilman Dr., La Jolla, CA, 92093, MC 2385, USA.
7
Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil.
8
University of São Paulo, Institute of Biomedical Science, Department of Microbiology, Laboratory of Stem Cell and Disease Modeling, São Paulo, SP, 05508-000, Brazil.
9
University of São Paulo, School of Arts Sciences and Humanities, Department of Obstetrics, São Paulo, SP, 03828-000, Brazil.
10
University of São Paulo, School of Medicine, Center for Cellular and Molecular Therapy (NETCEM), São Paulo, SP, 01246-903, Brazil.
11
Division of Inflammation Biology, La Jolla Institute for Allergy & Immunology, La Jolla, CA, 92037, USA.
12
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
13
University of São Paulo, Institute of Biomedical Science, Department of Microbiology, Laboratory of Stem Cell and Disease Modeling, São Paulo, SP, 05508-000, Brazil. patriciacbbbraga@usp.br.
14
University of São Paulo, School of Arts Sciences and Humanities, Department of Obstetrics, São Paulo, SP, 03828-000, Brazil. patriciacbbbraga@usp.br.
15
University of São Paulo, School of Medicine, Center for Cellular and Molecular Therapy (NETCEM), São Paulo, SP, 01246-903, Brazil. patriciacbbbraga@usp.br.
16
Sanford Burnham Prebys Medical Discovery Institute, 10901N. Torrey Pines Rd., La Jolla, CA, 92037, USA. terskikh@sbpdiscovery.org.
17
University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, La Jolla, CA, 92037-0695, USA. muotri@ucsd.edu.

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.

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