Journal Article

Therapeutic efficacy of favipiravir against Bourbon virus in mice

Zhao, Guoyan, Williams, Graham D., Bailey, Thomas, Diamond, Michael S., Janowski, Andrew B., Kwon, Jennie H., Shafiuddin, Md, Boon, Adrianus C. M., Jagger, Brett W., Wang, David, Bricker, Traci L., Gounder, Anshu P.

2019

Overview

Bourbon virus (BRBV) is an emerging tick-borne RNA virus in the orthomyxoviridae family that was discovered in 2014. Although fatal human cases of BRBV have been described, little is known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a fatal case in 2017 and successfully recovered the second human infectious isolate of BRBV. Next-generation sequencing of the St. Louis isolate of BRBV (BRBV-STL) showed >99% nucleotide identity to the original reference isolate. Using BRBV-STL, we developed a small animal model to study BRBV-STL tropism in vivo and evaluated the prophylactic and therapeutic efficacy of the experimental antiviral drug favipiravir against BRBV-induced disease. Infection of Ifnar1-/- mice lacking the type I interferon receptor, but not congenic wild-type animals, resulted in uniformly fatal disease 6 to 10 days after infection. RNA in situ hybridization and viral yield assays demonstrated a broad tropism of BRBV-STL with highest levels detected in liver and spleen. In vitro replication and polymerase activity of BRBV-STL were inhibited by favipiravir. Moreover, administration of favipiravir as a prophylaxis or as post-exposure therapy three days after infection prevented BRBV-STL-induced mortality in immunocompromised Ifnar1-/- mice. These results suggest that favipiravir may be a candidate treatment for humans who become infected with BRBV.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amides - pharmacology / Analysis / Animal models / Animals / Antiviral agents / Antiviral Agents - pharmacology / Arachnids / Bendamustine / Biological response modifiers / Biology and Life Sciences / Biopsy / Care and treatment / Chlorocebus aethiops / Disease Models, Animal / Disease prevention / Favipiravir / Fever / Hospitals / Humans / Hybridization / Immunology / In vivo methods and tests / Infections / Infectious diseases / Influenza / Interferon / Internal medicine / Liver / Lymphoma / Lymphomas / Medicine / Medicine and Health Sciences / Mice / Mice, Knockout / Next-generation sequencing / Nucleotides / Orthomyxoviridae Infections - genetics / Orthomyxoviridae Infections - immunology / Orthomyxoviridae Infections - pathology / Orthomyxoviridae Infections - prevention & control / Pathogenesis / Pathology / Prevention / Prophylaxis / Pyrazines - pharmacology / Receptor, Interferon alpha-beta - deficiency / Receptor, Interferon alpha-beta - immunology / Research and Analysis Methods / Risk factors / RNA / RNA polymerase / RNA virus infections / RNA viruses / Spleen / Thogotovirus - immunology / Thogotovirus - pathogenicity / Tick-borne diseases / Treatment outcome / Tropism / Vaccines / Vero Cells / Viral Tropism - drug effects / Viral Tropism - genetics / Viral Tropism - immunology / Viruses