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 ...