Disease relevance of HN

• Here we present the crystal structures of Newcastle disease virus HN alone and in complex with either an inhibitor or with the beta-anomer of sialic acid [1].
• Solubilization of HN spikes can be achieved by treatment of virions with detergent and high salt concentrations [2].
• The three-dimensional structure of the haemagglutinin-neuraminidase (HN) from a human parainfluenza virus is described at ca 2.0 A resolution, both in native form and in complex with three substrate analogues [3].
• Thus, the influenza virus HA protein will not substitute for the NDV HN protein in cell-to-cell fusion [4].
• The oligosaccharide side chains of HN were modified very slowly in chick cells, whereas those of the G glycoprotein of vesicular stomatitis virus were rapidly processed to a complex form [5].

High impact information on HN

• The HN glycoprotein has a single sequence near the amino terminus that functions as both a signal-sequence and a transmembrane-spanning segment [6].
• Surprisingly, the majority of the HN nascent chain remained ribosome associated after puromycin treatment [6].
• We have examined the requirement for ribonucleotides and ribonucleotide triphosphate hydrolysis during early events in the membrane integration of two membrane proteins: the G protein of vesicular stomatitis virus and the hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus [6].
• A cloned full-length copy of the genome of the lentogenic NDV strain Clone 30 was used for insertion of the ORF encoding the HA of the highly pathogenic AIV isolate A/chicken/Italy/8/98 (H5N2) in the intergenic region between the NDV fusion and hemagglutinin-neuraminidase (HN) genes [7].
• Using reverse genetics, we constructed a chimeric avian influenza virus that expressed the ectodomain of the hemagglutinin-neuraminidase gene of NDV instead of the neuraminidase protein of the H5N1 avian influenza virus [8].

Chemical compound and disease context of HN

• Monoclonal antibodies as functional probes of the HN glycoprotein of Newcastle disease virus: antigenic separation of the hemagglutinating and neuraminidase sites [9].
• In addition, the products contain a polypeptide (67K) that migrates on polyacrylamide gels slightly faster than the HN protein from virions [10].
• For human parainfluenza type 3, one bifunctional site on HN can carry out both binding and neuraminidase, and the receptor mimic, zanamivir, impairs viral entry by blocking receptor binding [11].
• Using biotin-labeled peptides with sequences of the Newcastle disease virus (NDV) F protein heptad repeat 2 (HR2) domain, we detected a specific interaction with amino acids 124 to 152 from the NDV HN protein [12].
• The role of the individual cysteine residues in the formation of the mature, antigenic HN protein of Newcastle disease virus [13].

Biological context of HN

• This site may provide both sialic acid binding and hydrolysis functions since there is no evidence for a second sialic acid binding site in HN [1].
• Creation of the second binding site on hPIV1 HN, however, did not significantly affect the growth or fusion activity of the recombinant virus [14].
• In this study, the role of the HN gene in NDV virulence was examined [15].
• Loss of glycosylation does not affect the receptor recognition by HN glycoprotein of NDV [16].
• Most paramyxovirus fusion (F) proteins require the coexpression of the homologous attachment (HN) protein to promote membrane fusion, consistent with the existence of a virus-specific interaction between the two proteins [17].

Anatomical context of HN

• Signal recognition particle in the absence of membranes inhibited HN protein synthesis [18].
• Comparisons of the trypsin digestion products of the HN protein made in the cell-free system with newly synthesized HN protein from infected cells showed that the cell-free product was in a conformation different from that of the pulse-labeled protein in infected cells [18].
• These results show that a single amino acid change in the F(1) portion of the NDV F protein can alter the stringent requirement for HN protein expression in syncytium formation [19].
• This antibody also inhibited the fusion of red blood cells to cells expressing F and HN proteins [20].
• The major site of accumulation of mature HN with neuraminidase activity was the plasma membrane [5].

Associations of HN with chemical compounds

• Second, trypsin digestion of Triton X-100-permeabilized membranes isolated from infected cells resulted in a 67,000-dalton trypsin resistant HN protein fragment [18].
• It migrates in nonreducing gels and sediments in sucrose gradients at the rate expected for homodimeric HN [2].
• It is membrane anchor-less, due to removal of a 14-kDa fragment from the NH2 terminus of HN [2].
• The hPIV1 HN with Asp at position 523 hemagglutinated in the presence of BCX-2798, suggesting that the amino acid difference at position 523 is critical for the formation of a second binding site [14].
• Biotin-labeled HR2 peptides bound to glutathione S-transferase (GST) fusion proteins containing these HN protein sequences but not to GST or to GST containing HN protein sequences corresponding to amino acids 49 to 118 [12].

Other interactions of HN

• Monoclonal antibodies to the haemagglutinin-neuraminidase (HN), fusion (F), polymerase and nucleocapsid polypeptides of Newcastle disease virus were prepared [21].
• The existence of these transcripts yields a transcription map order of NP, P, M, F0, HN [22].

Analytical, diagnostic and therapeutic context of HN

• To verify the functional significance of the interaction, two point mutations in the HN protein gene, I133L and L140A, were made individually by site-specific mutagenesis to produce two mutant proteins [12].
• Vaccination by the ocular route with a mixture of fowlpox recombinants expressing the fusion and HN proteins did not show added protection over that seen with the individual viruses [23].
• The patterns of cross-reactivity of the HN proteins of these mutants against the collection of MAbs determined by Western blotting allowed the MAbs to be sorted into different groups [24].
• In addition, the mobility of the haemagglutinin-neuraminidase protein, HN, was decreased on non-reduced SDS-PAGE in this mutant [25].
• Immunoprecipitation with chicken anti-NDV serum confirmed authentic expression of the HN protein [23].

References