Abstract and Introduction

Abstract

The emergence of SARS-CoV-2 and the worldwide COVID-19 pandemic triggered considerable attention to the emergence and evolution of novel human pathogens. Bourbon virus (BRBV) was first discovered in 2014 in Bourbon County, Kansas, USA. Since its initial discovery, several cases of BRBV infection in humans have been identified in Kansas, Oklahoma, and Missouri. BRBV is classified within the Thogotovirus genus; these negative-strand RNA viruses appear to be transmitted by ticks, and much of their biology remains unknown. In this review, we describe the emergence, virology, geographic range and ecology, and human disease caused by BRBV and discuss potential treatments for active BRBV infections. This virus and other emerging viral pathogens remain key public health concerns and require continued surveillance and study to mitigate human exposure and disease.

Introduction

The first case of Bourbon virus (BRBV) was identified in June 2014 in Bourbon County, Kansas, USA, after severe febrile illness developed in a previously healthy middle-aged (>50 years of age) man^[1]. Several days after he removed an engorged tick from his shoulder, nonspecific symptoms of disease appeared. After 3 days of worsening fever, myalgia, arthralgia, and diarrhea, the patient visited his primary care physician and was prescribed doxycycline. The next day, the patient was admitted to the hospital because of dehydration, syncope, and a possible tickborne illness. Doxycycline treatment was continued; however, the patient did not respond, and symptoms continued to progress toward multiorgan failure. Laboratory results revealed progressive leukopenia and thrombocytopenia (which are now considered identifiers of potential BRBV infection). Patient blood samples tested negative for all known regional tickborne diseases. Therefore, a whole blood sample was sent to the US Centers for Disease Control and Prevention (CDC) to test for Heartland virus (HRTV), a similar emerging tickborne virus in the region. The index patient died 11 days after symptom onset.

Initial efforts at CDC to identify the causative agent of disease in this first case revealed heterologous (non-HRTV) viral plaques in plaque reduction neutralization tests performed by using serum from the deceased patient and including a control HRTV strain. Subsequent electron microscopy revealed pleiomorphic viral particles consistent with the family Orthomyxoviridae^[1]. Phylogenetic analyses revealed a close relationship between the patient’s novel virus and Thogoto and Dhori viruses, placing it within the genus Thogotovirus. Subsequent genetic analyses supported this initial genus classification^[2,3]. Recently, another novel thogotovirus (Oz virus) was discovered in ticks in Japan; this virus was capable of replicating in mammalian cell lines and is the closest known relative of BRBV^[3]. BRBV was the first human pathogen in the genus Thogotovirus identified in the Western Hemisphere; Aransas Bay virus, another pathogenic member of this genus, was reported in ticks found in seabird nests in the United States^[2]. Since its initial identification, ≥5 human cases of BRBV-associated disease have been reported in the Midwest region of the United States^[1,4–8]. Because little is known about BRBV biology and no specific treatments or vaccines are available, further studies of BRBV are needed.