Bunyavirales: Scientific Gaps and Prototype Pathogens for a Large and Diverse Group of Zoonotic Viruses

Abstract

Research directed at select prototype pathogens is part of the approach put forth by the National Institute of Allergy and Infectious Disease (NIAID) to prepare for future pandemics caused by emerging viruses. We were tasked with identifying suitable prototypes for four virus families of the Bunyavirales order (Phenuiviridae, Peribunyaviridae, Nairoviridae, and Hantaviridae). This is a challenge due to the breadth and diversity of these viral groups. While there are many differences among the Bunyavirales, they generally have complex ecological life cycles, segmented genomes, and cause a range of human clinical outcomes from mild to severe and even death. Here, we delineate potential prototype species that encompass the breadth of clinical outcomes of a given family, have existing reverse genetics tools or animal disease models, and can be amenable to a platform approach to vaccine testing. Suggested prototype pathogens outlined here can serve as a starting point for further discussions.

Favipiravir Treatment Prolongs Survival in a Lethal BALB/c Mouse Model of Ebinur Lake Virus Infection

“…To our knowledge, the immunocompetent animals infection model was only successfully developed for three orthobunyaviruses: Jamestown Canyon virus [ 28 ], Cache Valley virus [ 29 , 30 ] and Bunyamwera virus [ 30 ]. Most animal infection model were based on immunodeficient animals (e.g., interferon knockout) or immunologically immature animals (e.g., newborn, suckling, or weanling) [ 30 ], since the orthobunyaviruses they used do not cause disease in immunocompetent laboratory animals [ 31 ]. When studying pathogenesis in immunocompetent individuals, the immune system often plays a key role and may particularly influence virus infection or contributing to immunopathology, and it represents a more realistic and predictive context in which antiviral therapies can be tested [ 30 ].…”

SFTSV-Nluc: a useful tool for studying SFTSV biology and countermeasures

“…SFTSV's lethality in immunodeficient mice, newborn rats, STAT2 knockout hamsters, and aged ferrets has been reviewed by Hartman et al . 9 Given that immunodeficient A129 mice may not fully simulate an authentic human infection, in vivo potency of a selected antiviral shall be assured in different immunocompetent animals before entering IND and/or clinical trials. Nevertheless, SFTSV-Nluc may play a role in prioritizing a more suitable animal model for studying virus tropism, pathogenesis, and transmission.…”