A pegivirus associated with encephalitis in red-legged partridges shows neurotropism across avian species

Abstract

Abstract Pegiviruses are generally regarded as non-pathogenic viruses with controversial clinical significance. Here, we describe an avian pegivirus (partridge pegivirus, ParPgV) associated with field outbreaks of encephalitis in red-legged partridges ( Alectoris rufa ). Next-generation sequencing identified ParPgV in brain tissues, revealing two distinct avian-origin pegiviruses. Histopathology and electron microscopy revealed encephalitic lesions, neuronal degeneration, and viral particles within neurons. Field surveillance demonstrated widespread vertical transmission across multiple partridge flocks. Experimental inoculation of red-legged partridges, grey partridges, and specific-pathogen-free chickens demonstrated viral neurotropism and systemic distribution with differences in humoral immune response. Infected red-legged partridges developed cerebellar atrophy detectable by MRI. Detection of negative-strand RNA replication intermediates confirmed active viral replication across different experimental hosts, and RNAscope in situ hybridization and immunohistochemistry further confirmed viral RNA and antigen in neural and lymphoid tissues. Here, we show experimental evidence supporting an association between a pegivirus and encephalitis, and suggest underappreciated neuropathogenic potential.