Essential Role of Interferon Response in Containing Human Pathogenic Bourbon Virus

Jonas Fuchs; Tobias Straub; Maximilian Seidl; Georg Kochs

Disclosures

Emerging Infectious Diseases. 2019;25(7):1304-1313. 

In This Article

Abstract and Introduction

Abstract

Bourbon virus (BRBV) is a recently discovered tick-transmitted viral pathogen that is prevalent in the Midwest and southern United States. Since 2014, zoonotic BRBV infections have been verified in several human cases of severe febrile illness, occasionally with fatal outcomes, indicating a possible public health threat. We analyzed the pathology of BRBV infection in mice and found a high sensitivity of the virus to the host interferon system. Infected standard laboratory mice did not show clinical signs or virus replication. However, in mice carrying defects in the type I and type II interferon system, the virus grew to high titers and caused severe pathology. In cell culture, BRBV was blocked by antiviral agents like ribavirin and favipiravir (T705). Our data suggest that persons having severe BRBV infection might have a deficiency in their innate immunity and could benefit from an already approved antiviral treatment.

Introduction

In the past 4 years, several reports from the Midwest and southern United States have described the detection of a new viral pathogen, called Bourbon virus (BRBV), associated with severe febrile illness.[1–4] The isolation of BRBV from patients with a history of tick bites was unexpected, because BRBV belongs to tick-transmitted viruses of the genus Thogotoviruses, which are largely unknown in the United States. However, recent tick surveillance campaigns confirmed the prevalence of BRBV in the affected region.[5,6]

Thogotoviruses are influenza virus–like arboviruses with a segmented RNA genome; they are frequently isolated in Africa, the Middle East, Asia, and southern Europe and are usually associated with diseases in livestock.[7] BRBV is genetically most similar to Dhori virus (DHOV) from India.[8] Although serologic surveys suggest the occurrence of zoonotic transmission of Thogotoviruses, few human cases have been well-documented.[9,10] However, in laboratory mice, Thogotoviruses show an aggressive systemic infection affecting mainly the liver, lungs, and spleen, leading to a fatal acute hepatitis. This severe disease progression is accompanied by a massive induction of interferon (IFN) α without an apparent protective effect.[11,12]

We conducted our study with the aim to evaluate the virulence and pathogenesis of BRBV in vivo. Furthermore, we assessed the antiviral effect of the host IFN system on BRBV replication.

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