Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice.

Abstract

Zika fever, a mosquito-borne infectious disease caused by Zika virus (ZIKV), is an epidemic disease for which no effective therapy has been established. The recent outbreaks of ZIKV in Brazil and French Polynesia have been linked to a considerable increase in the incidence of fetal microcephaly and other diseases such as Guillain-Barre syndrome. Because there is currently no specific therapy or vaccine, the early exploitation of a method to prevent expansion of ZIKV is a high priority. To validate commonly used antiviral drugs, we evaluated the effect of ribavirin, a drug used to treat hepatitis C with interferon-β (IFN-β), on ZIKV replication. In mammalian cells, we observed an inhibitory effect of ribavirin on ZIKV replication and ZIKV-induced cell death without cytotoxic effect. Furthermore, we found that STAT1-deficient mice, which lack type I IFN signaling, were highly sensitive to ZIKV infection and exhibited lethal outcome. Ribavirin abrogated viremia in ZIKV-infected STAT-1-deficient mice. These data suggest that the inhibition of viral RNA-dependent RNA polymerases may be effective for treatment of ZIKV infection. Our data provide a new insight into the mechanisms for inhibition of ZIKV replication and prevention of Zika fever.

• Authors: Naganori Kamiyama, Ryusuke Soma, Shinya Hidano, Kei Watanabe, Hiroshi Umekita, Chiaki Fukuda, Kaori Noguchi, Yoshiko Gendo, Takashi Ozaki, Akira Sonoda, Nozomi Sachi, Lucky Ronald Runtuwene, Yumako Miura, Etsuro Matsubara, Shigeru Tajima, Tomohiko Takasaki, Yuki Eshita, Takashi Kobayashi
• Journal: Antiviral research (Antiviral Res) Vol. 146 Pg. 1-11 (Oct 2017) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 28818572 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• STAT1 Transcription Factor
• Stat1 protein, mouse
• Ribavirin

Topics

• Animals
• Antiviral Agents (administration & dosage, pharmacology, therapeutic use)
• Chlorocebus aethiops
• DNA Replication (drug effects)
• Mice
• Ribavirin (administration & dosage, pharmacology, therapeutic use)
• STAT1 Transcription Factor (deficiency, genetics)
• Vero Cells
• Viremia (drug therapy, virology)
• Virus Replication (drug effects)
• Zika Virus (drug effects, physiology)
• Zika Virus Infection (drug therapy, virology)