Mumps virus hemagglutinin-neuraminidase protein (HN protein)

The **Mumps virus hemagglutinin-neuraminidase protein** (HN protein) is a multifunctional viral surface glycoprotein essential for mumps virus infectivity and pathogenesis. It is a type II membrane protein with an N-terminal cytoplasmic tail and an extracellular C-terminal domain, assembled as a homotetramer with a characteristic six-bladed β-propeller head structure[3]. The HN protein exhibits both hemagglutinin (receptor binding) and neuraminidase (sialidase) activities in a single polypeptide, mediating viral attachment by recognizing α2,3-linked sialic acid-containing receptors—primarily unbranched trisaccharides—on host cells[2][3][9]. After binding, conformational changes in HN trigger activation of the viral fusion (F) protein, promoting membrane fusion for viral entry and cell-to-cell spread[3][6][7]. Neuraminidase activity further enables viral release from host cells by cleaving sialic acid residues, preventing self-aggregation of virions and promoting efficient spread. Variations in HN structure and glycan-receptor preference contribute to viral tissue tropism, including glandular tissue and central nervous system involvement[2][3][4][9]. HN is a major antigenic target for neutralizing antibodies and is crucial for vaccine efficacy, but genetic variation can contribute to both vaccine failures and altered pathogenicity, including neurovirulence in certain attenuated strains[5][8][9]. The HN protein is considered an attractive but as-yet unexploited therapeutic target for small-molecule inhibitors[1][7].

Other names

Mumps virus HN proteinMuV-HNHemagglutinin-neuraminidase (HN)Hemagglutinin-neuraminidase glycoprotein

Inhibitors would act by blocking sialic acid binding, neuraminidase catalytic activity, or protein conformational changes required for membrane fusion and viral entry[1][7][9]