# Fatal H5N1 Highly Pathogenic Avian Influenza with Retrograde Neuroinvasion in a Free-Ranging Leopard Cat (Prionailurus bengalensis) During a Wild Bird Outbreak in South Korea

## TL;DR

A leopard cat in South Korea died from H5N1 bird flu, showing how wild animals can catch and spread the virus from birds.

## Contribution

First documented case of fatal H5N1 infection in a free-ranging leopard cat with evidence of retrograde neuroinvasion.

## Key findings

- HPAI H5N1 caused severe neurological and respiratory disease in a leopard cat.
- Viral antigen was detected in the brain and nasal passages, indicating dual routes of viral spread.
- Leopard cats may serve as sentinels for avian influenza spillover in wetland ecosystems.

## Abstract

Highly pathogenic avian influenza (HPAI) H5N1 viruses carried by migratory wild birds have recently caused large outbreaks and unusual spillover infections in wild and domestic mammals. The leopard cat (Prionailurus bengalensis) is an endangered small wild felid in South Korea that inhabits wetland–forest ecotones and frequently overlaps with wild waterbirds, making it a potential sentinel for avian influenza circulation. This case report describes a free-ranging leopard cat that died from HPAI H5N1 clade 2.3.4.4b infection and was detected through the national wildlife disease surveillance program during a period of intense H5N1 activity in wild birds along the East Asian–Australasian Flyway. Necropsy and histopathology revealed severe pneumonia, diffuse meningoencephalitis, vasculitis, and gastrointestinal and mesenteric lesions. Immunohistochemistry showed abundant viral antigen in the nasal and olfactory mucosa, olfactory bulb, brain, and respiratory epithelium, supporting combined olfactory and hematogenous dissemination. This case illustrates that wild carnivores can develop rapidly fatal disease following exposure to HPAI viruses maintained in wild birds and highlights the importance of integrated surveillance in wild birds and mammals for early detection of cross-species transmission at high-risk wetland interfaces.

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses spread efficiently via migratory wild birds and increasingly infect mammals. The leopard cat (Prionailurus bengalensis) is an endangered mesopredator in South Korea that frequents wetland–forest ecotones and overlaps with wild waterbirds, placing it at risk of exposure. We describe a fatal HPAI H5N1 infection in a free-ranging leopard cat detected through national wildlife surveillance during a period of widespread H5N1 activity in wild birds along the East Asian–Australasian Flyway. The animal showed acute neurological and respiratory signs and died shortly after rescue. H5 viral RNA was detected by RT-qPCR in all examined tissues, with the highest load in the brain, and infectious virus was isolated from the brain, bronchoalveolar lavage fluid, and nasal swab. Pathology revealed acute serofibrinous pneumonia, severe nonsuppurative meningoencephalitis, necrotizing vasculitis with thrombosis, and necrotizing enteritis with secondary mesenteritis. Immunohistochemistry demonstrated abundant viral antigen in nasal and olfactory epithelium, olfactory bulb, neurons, endothelial cells, and bronchial and bronchiolar epithelium, supporting combined olfactory and hematogenous dissemination. This clinicopathological description expands the spectrum of HPAI-associated lesions in felids and underscores the value of wild carnivores as bioindicators of avian influenza spillover in a One Health context.