Characterization of experimental Shuni virus infection in the mouse.

Summary

Shuni virus, an orthobunyavirus transmitted by blood-feeding insects, causes neurological disease in horses and cattle alongside reproductive losses in ruminants, with emerging evidence of zoonotic risk; however, its pathogenic mechanisms remain poorly understood. Breithaupt and colleagues utilised interferon-receptor-deficient mice (Ifnar⁻⁻) infected subcutaneously with two SHUV strains—one isolated from an affected heifer's brain and one naturally lacking the NSs protein, which normally suppresses the host's interferon response—to characterise target cells and neuropathological features. Both strains proved lethal in this model, producing meningoencephalomyelitis histologically consistent with naturally infected cattle, with in situ hybridisation identifying virus replication specifically in neurons, astrocytes, macrophages, and lymphoid tissue. The findings demonstrate that neurological vulnerability depends partly on viral evasion of interferon defences, as the NSs-deficient strain nonetheless caused severe disease despite impaired immune antagonism. For equine and livestock practitioners, this work provides mechanistic insight into SHUV neuroinvasion and validates a robust experimental model for testing preventive or therapeutic interventions—particularly relevant given the virus's expanding geographical range and increasing detection in previously unaffected regions.

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Key Findings

• •Ifnar-/- mice are susceptible to both SHUV strains and can develop fatal disease
• •Histological examination confirmed meningoencephalomyelitis in mice similar to natural cattle infections
• •Target cells for SHUV infection include neurons, astrocytes, macrophages in spleen and gut-associated lymphoid tissue
• •NSs protein deletion mutant strain demonstrated altered virulence patterns in the mouse model

Conditions Studied

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