Therapeutic efficacy of #favipiravir against #Bourbon virus in mice (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Therapeutic efficacy of favipiravir against Bourbon virus in mice

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

Published: June 13, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1007790

 

Abstract

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.

 

Author summary

Bourbon virus (BRBV) is a novel tick-borne RNA virus that can cause fatal disease in humans. No approved antiviral treatment is available. We have cultured the second human isolate of BRBV and with it developed a small animal disease model. In this mouse model, BRBV causes severe disease as measured by weight loss after infection and uniform death 6 to 10 days after infection. Virus replication occurred predominantly in the spleen and the liver of the infected animals, with additional organs infected at later time points after infection. This disease model was used to test the efficacy of favipiravir, a viral RNA polymerase inhibitor that was developed for the related Influenza A virus. Prophylactic and therapeutic treatment with favipiravir resulted in complete protection from a lethal BRBV infection. These data suggest that favipiravir and perhaps other RNA polymerase inhibitors could be used to treat BRBV infections in humans.

___

Citation: Bricker TL, Shafiuddin M, Gounder AP, Janowski AB, Zhao G, Williams GD, et al. (2019) Therapeutic efficacy of favipiravir against Bourbon virus in mice. PLoS Pathog 15(6): e1007790. https://doi.org/10.1371/journal.ppat.1007790

Editor: Sonja Best, National Institute of Allergy and Infectious Diseases, UNITED STATES

Received: February 6, 2019; Accepted: April 26, 2019; Published: June 13, 2019

Copyright: © 2019 Bricker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The genome sequence of Bourbon virus: All sequence files are available from the GenBank database (accession number(s) MK453524-MK453529). All other relevant data are within the manuscript and its supporting information files.

Funding: The work was in part funded by R01-AI118938, and R21-AI137450 and the Children’s Discovery Institute grant PD-II-2018-702. APG and GDW were supported by the Infectious Disease Training Grant (T32 AI007172). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Bourbon virus; Viral pathogenesis; Antivirals; Favipiravir; Animal models.

—–

Advertisements

Published by

gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s