Hematogenous #neuroinvasion and genotype-dependent #transmission of #influenza A #H5N1 viruses in the #cat host
Abstract The spillover of highly pathogenic avian influenza (HPAI) A H5N1 virus to mammalian hosts raises major concerns due to its pandemic potential . Cats are frequently affected mammals, often succumbing to systemic and neurological disease . Here, we characterized the pathogenesis and transmissibility of two H5N1 genotypes, B3.13 and D1.1, in cats . Infected cats exhibited high-level viremia and virus shedding in nasal, oral, and fecal secretions were consistently detected. The virus replicated initially in the upper respiratory tract and lungs , followed by systemic dissemination and neuroinvasion . Notably, the virus crossed the blood-brain-barrier by infecting endothelial cells , spreading to astrocytes and neurons , causing multifocal encephalitis . D1.1-virus infection caused protracted disease with lower shedding and no transmissibility , whereas B3.13 virus caused rapid onset with efficient shedding and transmission. These findings reveal critical H5N1 neuropathogenes...