#19,063
Based on limited - and admittedly opportunistic - surveillance, felines (domestic cats, mountain lions, bobcat, etc.) are (excluding dairy cattle) the non-human mammalian species which are most often reported to be infected with HPAI H5N1.
How many fox, skunk, or mice that are actually infected in the wild is unknown. But cats have a known history of susceptibility to the virus (see 2023's A Brief History Of Avian Influenza In Cats).
Over the years we've seen plenty of evidence of Differences In Virulence Between Closely Related H5N1 Strains, with stark differences in mortality rates reported by countries around the world (see chart below).
While there are scores of H5N1 genotypes currently in circulation (and different subclades in India and Cambodia), among clade 2.3.4.4b viruses, two genotypes currently stand out in North America; `Bovine' B3.13 and avian D1.1.
Both have been reported in poultry, dairy cattle, and humans, but the B3.13 appears to be more at home in dairy cattle, while D1.1 is particularly prevalent in wild birds and poultry.
B3.13 appears to be milder in humans than D1.1, although that is based on a relatively small sample. Neither genotype approach the virulence, however, of many older H5N1 strains or the current clade 2.3.2.1e in Cambodia.
But H5Nx viruses continues to evolve, and the threats we may face tomorrow may be far different.
Today we've a preprint from researchers at Cornell University in NY state, which looks at the course of infection, virulence, and transmissibility of SPF (specific pathogen-free) lab cats when infected with B3.13 and D1.1 genotypes of H5N1.
Notably, while we've seen prior evidence suggesting that genotype D1.1 is more problematic in humans (see J.I.D.: Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13), this report finds the opposite seems to be true in cats.
B3.13 infection produced faster disease progression, greater shedding, higher mortality, and efficient (75%) direct contact transmission. Whereas D1.1 infected cats saw slower progression, lower mortality, and no evidence of direct contact transmission.
Of note: only two isolates were tested; B3.13 from bovine (TX224) with PB2 M631L mammalian adaptation, and D1.1 from a strictly avian source (NY314925).
Given the diversity of viruses within each genotype, there are limits to how much we can assume based on this study. A D1.1 virus isolated from a mammalian source might well have performed differently.
Nevertheless, this is a fascinating, and highly detailed, look at the pathogenesis of two frontrunning H5N1 genotypes in cats, which suggests that B3.13 is better adapted to the feline host.
Due to its length, and complexity, I've only posted the abstract and a brief excerpt from the preprint. Follow the link to read it in its entirety.
Hematogenous neuroinvasion and genotype-dependent transmission of influenza A H5N1 viruses in the cat host
Salman L. Butt, Ruchi Rani, Mohammed Nooruzzaman, Elena A. Demeter, Pablo S.B. de Oliveira, Gavin R. Hitchener, Diego G. Diel
doi: https://doi.org/10.64898/2026.02.21.707182
This article is a preprint and has not been certified by peer review
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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 neuropathogenesis mechanisms and highlight mammalian transmission potential in a species with close human contact.
(SNIP)
The primary concern regarding the rapid genetic diversification observed in H5N viruses is the potential emergence of variants with enhanced transmissibility or pathogenicity. Epidemiological evidence indicates that both H5N1 genotypes B3.13 and D1.1 exhibit improved fitness when compared to their ancestral strains.
The B3.13 genotype successfully spilled over into dairy cattle, establishing efficient transmission chains within this novel host species and subsequently spreading to other mammalian- (including humans and cats) and avian hosts.
Similarly, the D1.1 genotype emerged in wild birds, causing the largest infection wave since the introduction of H5N1 in North America. This genotype also crossed the species barrier, jumping from wild birds to dairy cows in three independent spillover events across Nevada, Arizona, and Wisconsin.
(SNIP)
Collectively, our results suggest that differences in the polymerase activities between B3.13 (TX2/24) and D1.1 (NY3149/25) viruses may contribute to their distinct abilities to replicate and transmit in the cat host.Further investigations are needed to determine whether both viruses replicate to similar levels in avian hosts in vivo. Our study revealed critical aspects of H5N1 virus pathogenesis in a naturally susceptible animal species, emphasizing the risk posed by B3.13 viruses currently circulating in dairy cattle in the U.S. and frequently transmitted to cats.
