Influenza A viruses (IAVs) pose a serious risk to both human and animal health. IAVs' receptor binding characteristics account for a major portion of their host range and tissue tropism. While the function of neuraminidase (NA) in promoting the release of progeny virus is well-known, its role in the virus entry process remains poorly understood. Studies have suggested that certain subtypes of NA can act as receptor-binding proteins, either alone or in conjunction with haemagglutinin (HA). An important distinction is that NA from the avian influenza virus have a second sialic acid-binding site (2SBS) that is preserved in avian strains but missing in human or swine strains. Those observations suggest that the 2SBS may play a key role in the adaptation of the avian influenza virus to mammalian hosts. In this review, we provide an update of the recent research advances in the receptor-binding role of NA and highlight its underestimated importance during the early stages of the IAV life cycle. By doing so, we aim to provide new insights into the mechanisms underlying IAV host adaptation and pathogenesis.
Keywords: Neuraminidase; avian influenza virus; host adaptation; influenza a virus; interspecies transmission; second sialic acid-binding site.