Abstract

Nairobi sheep disease orthonairovirus (NSDV) is a zoonotic tick-borne arbovirus, which causes severe gastroenteritis in small ruminants. To date, the virus is prevalent in East Africa and Asia. However, due to climate change, including the spread of transmitting tick vectors and increased animal movements, it is likely that the distribution range of NSDV is enlarging. In this project, sheep and cattle (hitherto classified as resistant to NSDV) were experimentally infected with NSDV for a comparative study of the species-specific pathogenesis. For this purpose, several new diagnostic assays (RT-qPCR, ELISA, iIFA, mVNT, PRNT) were developed, which will also be useful for future epidemiological investigations. All challenged sheep (three different doses groups) developed characteristic clinical signs, transient viremia and virus shedding—almost independent on the applied virus dose. Half of the sheep had to be euthanized due to severe clinical signs, including hemorrhagic diarrhea. In contrast, the course of infection in cattle was only subclinical. However, all ruminants showed seroconversion—implying that, indeed, both species are susceptible for NSDV. Hence, not only sheep but also cattle sera can be included in serological monitoring programs for the surveillance of NSDV occurrence and spread in the future.

Highlights

  • Nairobi sheep disease orthonairovirus (NSDV) is the eponymous representative of the family Nairoviridae within the order Bunyavirales [1]

  • Due to its zoonotic impact, NSDV is classified as a biosafety level (BSL) 3 agent, but reports of human infections resulting in febrile illnesses are scarce [3,4,5]

  • Our study revealed that the virus is shed via the respiratory and alimentary tract, as nasal and rectal swabs of sheep contained high amounts of NSDV RNA

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Summary

Introduction

Nairobi sheep disease orthonairovirus (NSDV) is the eponymous representative of the family Nairoviridae within the order Bunyavirales [1]. Causing severe gastroenteritis in small ruminants with case fatalities of 30–70% in susceptible populations, NSDV is part of the OIE list for notifiable animal diseases [2]. Due to its zoonotic impact, NSDV is classified as a biosafety level (BSL) 3 agent, but reports of human infections resulting in febrile illnesses are scarce [3,4,5]. The distantly related Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV, BSL 4) can induce fatal disease in humans. Leading both to hemorrhagic fevers in small ruminants and humans, NSDV has already been proposed as a model for human CCHFV infections [6,7]. The nucleocapsid protein (N) is encoded by the small (S) segment, the glycoprotein precursor (GPC) by the medium (M) segment, and the RNA-dependent RNA polymerase by the large (L) segment, respectively [8,9]

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