Details

Autor(en) / Beteiligte

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

Titel

Therapeutic efficacy of favipiravir against Bourbon virus in mice

Ist Teil von

• PLoS pathogens, 2019-06, Vol.15 (6), p.e1007790-e1007790

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.