Infectious Diseases 2026

The spillover of highly pathogenic avian influenza (HPAI) A H5N1 to mammalian hosts has raised significant concerns regarding its pandemic potential. Domestic cats are frequently affected by these spillovers, often succumbing to severe systemic and neurological diseases. A new study provides critical insights into how the virus attacks the feline nervous system and highlights alarming differences in transmissibility between recent viral strains.
The research outlines the aggressive progression of the H5N1 virus within the cat host. The virus initially replicates in the upper respiratory tract before entering the bloodstream to establish severe viremia. From the blood, it rapidly disseminates to multiple organ systems, including the lungs, liver, and lymphoid tissues, causing widespread cellular damage.
Perhaps the most critical discovery is the exact mechanism by which H5N1 causes neurological devastation. The study reveals that the virus uses a hematogenous (blood-borne) route to reach the central nervous system. It successfully crosses the blood-brain barrier by first infecting the endothelial cells that line the brain's blood vessels. Once across this barrier, the virus spreads to adjacent astrocytes and ultimately infects neurons, resulting in multifocal encephalitis.
To understand the evolving threat, researchers compared two distinct H5N1 genotypes currently circulating in North America: the B3.13 variant (which emerged in US dairy cattle in early 2024) and the D1.1 variant (an avian-derived strain).
The experimental results revealed stark differences in how these two strains behave in mammals: 
-Genotype B3.13 (Cattle-Derived): This variant caused rapid disease onset and severe symptoms in infected cats. It resulted in high levels of infectious viral shedding in nasal, oral, and fecal secretions. Most alarmingly, the B3.13 virus demonstrated efficient direct transmission to healthy contact cats. Laboratory tests also showed this variant has enhanced replication capabilities in mammalian cells due to higher viral polymerase activity.  
-Genotype D1.1 (Avian-Derived): Infections with this variant resulted in a more protracted, delayed disease course. It produced significantly lower levels of viral shedding compared to B3.13. Crucially, the D1.1 virus showed absolutely no transmissibility to healthy contact cats.
These findings confirm that the cattle-linked B3.13 genotype possesses enhanced fitness and transmission potential in mammalian hosts. By mapping out the precise mechanisms of H5N1 neuropathogenesis and proving that certain reassortant strains can transmit efficiently between mammals, this research highlights a growing public health risk for species that live in close contact with humans.