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Showing posts from February 23, 2026

The #bovine mammary #gland as a crucible for zoonotic #influenza virus emergence: Receptor-mediated #adaptation of HPAI #H5N1 clade 2.3.4.4b

  Abstract The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in U.S. dairy cattle marks a pivotal shift in the ecology of influenza A viruses (IAVs), signaling an unexpected expansion into a major livestock species . This review explores the molecular mechanisms underpinning this cross-species transmission , focusing on the unique sialic acid receptor landscape of the bovine mammary gland as a critical determinant. We synthesize emerging evidence that this tissue, which co-expresses both avian-type (α2,3-linked) and human-type (α2,6-linked) sialic acid receptors , functions as a novel biological crucible for viral adaptation . Within this environment, H5N1 virus faces selective pressure for hemagglutinin (HA) mutations —such as Q226L and N193D—that can alter receptor binding specificity toward human-like glycans , potentially bridging the species barrier. Recent studies confirm that bovine H5N1 virus isolates exhibit dual receptor-binding avidity ...

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...