Disease relevance of HN

• The nucleotide sequence of the haemagglutinin-neuraminidase (HN) gene was determined for a simian (W3), human (LN) and two canine (CPI+/CPI-) isolates of simian virus 5 (SV5) [1].
• It is suggested that, like the influenza virus neuraminidase, hemagglutinin-neuraminidase of paramyxoviruses is oriented with its N terminus inserted into the membrane [2].
• We report the crystal structures of the parainfluenza virus 5 (SV5) HN and its complexes with sialic acid, the inhibitor DANA, and the receptor sialyllactose [3].
• This led to the finding that the vast majority of HN expressed at the cell surface, rather than being incorporated into budding virions, is internalized and degraded after localization to endocytic vesicles and lysosomes [4].
• Comparison of the F and HN glycoproteins of Sendai virus with those of simian virus 5 strongly suggests that the cysteine residues are highly important for maintenance of the molecular structures of these glycoproteins [5].

High impact information on HN

• The effects of monospecific antibodies to the viral glycoprotein with hemagglutinating and neuraminidase activity (HN) and the viral glycoprotein with membrane-fusing activity (F) of the paramyxovirus simian virus 5 (SV5) on the spread of infection in two cell types have been investigated [6].
• In these cells, antibodies specific for the HN glycoprotein prevented the dissemination of infection by released infectious virus, but spread by cell fusion was not inhibited [6].
• The temperature dependence of fusion by F suggests that thermal energy, destabilizing proline residues and receptor binding by the hemagglutinin-neuraminidase (HN) protein collectively contribute to F activation from a metastable native state [7].
• The characteristic cleavage of SV5 HN in the late endosome distinguishes internalization from transport to later stages of the endocytic pathway [8].
• The intracellular assembly and transport of HN in CV1 cells was examined using conformation-specific HN mAbs and sucrose density sedimentation analysis [4].

Chemical compound and disease context of HN

• Structural studies of the parainfluenza virus 5 hemagglutinin-neuraminidase tetramer in complex with its receptor, sialyllactose [3].
• The presence of viral antigen in brain tissue was analyzed with the immunofluorescence technique employing monoclonal antibodies against nucleoprotein (NP), polymerase (P), matrix (M), hemagglutinin-neuraminidase (HN) and fusion (F) mumps virus components [9].
• The calculated molecular mass (64 kDa) of the protein is in good agreement with that of the unglycosylated HN protein (63 kDa) identified in tunicamycin treated mumps virus infected cells (Herrler and Compans, 1983) [10].
• The Hemagglutinin-Neuraminidase (HN) from the LPMV strain of Porcine rubulavirus was purified from virions by ultracentrifugation in a continuous 20-60% sucrose gradient and by ion exchange chromatography [11].
• The Hemagglutinin-Neuraminidase (HN) from 'La Piedad, Michoacan' porcine rubulavirus (LPMV) interacts specifically with NeuAc alpha 2,3 lactose residues on the target cell [12].

Biological context of HN

• The paramyxovirus hemagglutinin-neuraminidase (HN) functions in virus attachment to cells, cleavage of sialic acid from oligosaccharides, and stimulating membrane fusion during virus entry into cells [3].
• The F and HN proteins synthesized in recombinant infected cells are indistinguishable in terms of electrophoretic mobility and glycosylation from the proteins synthesized in simian virus 5-infected cells [13].
• cDNAs encoding the mRNAs for the fusion protein (F) and the hemagglutinin/neuraminidase protein (HN) of the paramyxovirus simian virus 5 have been inserted into a eukaryotic expression vector under the control of the simian virus 40 late promoter [13].
• In addition, the expressed F and HN proteins have been shown to be anchored in the plasma membrane in a biologically active form by indirect live cell immunofluorescence, the F-mediated formation of syncytia, and the ability of HN to cause the hemadsorption of erythrocytes to the infected cell surface [13].
• The F and HN proteins of all these viruses, including SV5 and NDV, however, were shown to have protein-specific structures as well as short but well-conserved amino acid sequences, suggesting that these structures and sequences are related to the activities of these glycoproteins [14].

Anatomical context of HN

• The HN molecules which were misfolded, owing to their altered glycosylation pattern, were retained in the endoplasmic reticulum [15].
• The inhibition of the pinching-off of coated pits from the plasma membrane by cytosol acidification significantly reduced HN internalization [16].
• The L539, 548A mutant also showed extensive syncytium formation when expressed without the SER virus HN protein [17].
• A hybridoma cell line secreting antibody of the immunoglobulin G3 isotype with kappa light chains and with activity against the HN glycoprotein of the Kilham strain of mumps virus was established [18].
• The expressed HN protein was transported to the cell surface and adsorbed guinea pig erythrocytes [19].

Associations of HN with chemical compounds

• A truncated form of HN, HNT (molecular weight, 63,000), was synthesized in the presence of tunicamycin and was also recognized only by group I antibodies [20].
• In contrast, group II antibodies, which preferentially recognized native virus in the enzyme-linked immunosorbent assay, reacted with native HN but failed to bind HN after sodium dodecyl sulfate denaturation [20].
• Deletion of groups of four of aa 478-485, single alanine, or other amino acid substitutions among aa 478-485 had minimal or limited effects on HPIV2 F/HN-induced cell fusion [21].
• A cell-surface-expressed chimeric protein (APK), consisting of the cytoplasmic tail, transmembrane (TM) domain, and 12 residues of the ectodomain of HN joined to the cytoplasmic protein pyruvate kinase is internalized, indicating that the N-terminal region of HN contains an internalization signal [22].
• A glutamic acid residue (E37) that abuts this presumptive HN TM domain/ectodomain boundary is important for SV5 HN internalization [22].

Other interactions of HN

• Chimeric SV5 minigenomes were constructed to contain exchanges of a 10 base gene end sequence and the U tract from the M-F (approximately 40% readthrough) and SH-HN (approximately 15% readthrough) junctions [23].

Analytical, diagnostic and therapeutic context of HN

• The sites of N-linked glycosylation on HN were identified by eliminating each of the potential sites for N-linked glycosylation by oligonucleotide-directed mutagenesis on a cDNA clone [15].
• Immunogold staining of HN on the surface of SV5-infected CV-1 cells and examination using electron microscopy, showed heavy surface labeling that gradually decreased with time [16].
• The deduced protein sequence was confirmed by limited N-terminal amino acid microsequencing of CNBr cleavage fragments of native HN that was purified by immunoprecipitation [24].
• Cell fusion was also observed when separate cell cultures were transfected with the HN and F genes and the F-expressing cells were mixed with the HN-expressing cells [25].
• Sequence determination of the mumps virus HN gene [26].

References