Disease relevance of HN

• In addition, the abnormal virus-like particles, of which HN protein and nucleocapsid were ablated, were released in the culture medium at 41 degrees C, although the size was smaller than the normal viral virions [1].
• Sequence determination of the Sendai virus HN gene and its comparison to the influenza virus glycoproteins [2].
• Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV and HPIV3 [3].
• Using recombinant vaccinia viruses to selectively express combinations of Sendai virus F, HN, and M proteins, we have successfully reconstituted M protein-glycoprotein interaction in vivo and determined the molecular interactions which are necessary and sufficient to promote M protein-membrane binding [4].
• The significance of these results with regard to the actions of HN protein and possible reasons for the selective killing of SSPE cells are discussed [5].

High impact information on HN

• Amino acid sequence comparisons of the SV HN and the FLU HA and NA proteins revealed homologies between 100 amino acids of the hemagglutinin region of the FLU HA protein and the C terminus of the SV HN, and between 200 amino acids of the neuraminidase region of the FLU NA and the central region of SV HN [2].
• The nucleotide sequence of the Sendai virus (SV) HN (hemagglutinin-neuraminidase) gene was determined [2].
• These results suggested the presence of a previously uncharacterized, HN-dependent intermediate stage in the Sendai virus-mediated membrane fusion [6].
• We have found that heated virus (56 degrees C, boiled or autoclaved) with no fusion and hemagglutinin-neuraminidase activities, behaves similar to live SV in T2kb cells by entering a TAP-independent and BFA-resistant pathway [7].
• To explore the mechanism that gives rise to this requirement, we have now investigated the distribution of Sendai virus envelope proteins (F, the fusion protein, and HN, the hemagglutinin/neuraminidase protein) on human erythrocytes in the course of fusion, using fluorescence microscopy and image analysis [8].

Chemical compound and disease context of HN

• Fusion of Sendai virus envelopes with erythrocyte membranes or with phosphatidylcholine/cholesterol liposomes requires the presence of the two viral glycoproteins, namely the hemagglutinin/neuraminidase (HN) and the fusion (F) polypeptides [9].
• Fragment A-containing liposomes associated with either hemagglutinating and neuraminidase (HN) or fusion (F) glycoprotein of HVJ (Sendai virus) were prepared [5].
• On the other hand, the fusogenic activity of the HN vesicles was not inhibited by treatment with dithiothreitol (DTT) or phenylmethanesulfonyl fluoride (PMSF), both of which are known to inhibit the Sendai virus fusogenic activity [10].
• The rotational mobility of Sendai virus envelope glycoproteins (F, the fusion protein, and HN, the hemagglutinin/neuraminidase) was determined by using erythrosin (ER)-labeled monovalent Fab' antibody fragments directed specifically against either F or HN [11].
• By the use of horseradish peroxidase-labelled Fab fragments of monoclonal antibodies, five major structural components of Sendai virus, namely the nucleocapsid (NP), polymerase (P), matrix (M), fusion (F), and haemagglutinin-neuraminidase (HN) proteins were localized in infected Vero cells [12].

Biological context of HN

• The results suggest that HN protein is necessary for viral morphogenesis [1].
• Lateral immobilization of varying fractions of F and/or HN (after virus adsorption and hemagglutination, but before fusion) was achieved by cross-linking them with succinyl concanavalin A (inhibiting both F and HN) or with specific rabbit IgG directed against either F or HN [13].
• Creation of the second binding site on hPIV1 HN, however, did not significantly affect the growth or fusion activity of the recombinant virus [14].
• The role of glycosylation and of disulfide bonds in the formation of the native structure of the Sendai virus hemagglutinin-neuraminidase (HN) and fusion (F0) glycoproteins was studied [15].
• In order to reduce the NTVLP formation with the aim of improving SeV for use as a vector for gene therapy, amino acid substitutions found in temperature-sensitive mutant SeVs were introduced into the M (G69E, T116A, and A183S) and HN (A262T, G264R, and K461G) proteins of SeV/deltaF to generate SeV/M(ts)HN(ts)deltaF [16].

Anatomical context of HN

• The results suggested that the specific interaction of HSP70 with HN protein prevented the protein from integrating into the cell membrane [1].
• Specific binding of heat shock protein 70 with HN-protein inhibits the HN-protein assembly in Sendai virus-infected Vero cells [1].
• Our results showed that M protein accumulates on cellular membranes via a direct interaction with both F and HN proteins [4].
• Using vaccinia virus recombinants expressing individual Sendai virus proteins, we found that the majority of these hybridomas (34 of 37) were specific for the hemagglutinin-neuraminidase (HN) glycoprotein [17].
• The mitogenic response of the HN and F glycoproteins has two components, a T cell-independent B cell proliferation, which is less than one-half of the total stimulation observed, and a T cell-dependent B cell proliferation [18].

Associations of HN with chemical compounds

• However, HN protein was not as present on the cell membrane following PGA1-treatment as it was at 41 degrees C, whereas F protein was detected [1].
• Membrane vesicles bearing only the HN or the F glycoprotein (HN or F vesicles) or a mixture of both do not possess fusogenic activity [9].
• Viral envelopes containing HN whose disulfide bonds were irreversibly reduced (HNred) were also prepared by treating the envelopes with dithiothreitol followed by dialysis (F,HNred-virosomes) [19].
• By desialylating the HepG2 cells, the entry mediated by HN-terminal sialic acid receptor interactions was bypassed [19].
• 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].

Analytical, diagnostic and therapeutic context of HN

• An immunoprecipitation assay showed that HSP70 was coprecipitated with HN protein, but not with F protein [1].
• Our results demonstrate that lateral immobilization of either F or HN results in a strong inhibition of cell-cell fusion and a much weaker inhibition of virus-cell fusion [13].
• Circular dichroism studies revealed that the conformation of the viral glycoproteins in reconstituted viral envelopes or in HN-F vesicles (vesicles formed by co-reconstitution of the HN and F glycoproteins) is different from that of the conformation of these glycoproteins in either HN or F vesicles or in a mixture of both [9].
• Furthermore, this cleavage product retained the antigenic structure of intact HN, since monoclonal antibodies still bound to C-HN in enzyme-linked immunosorbent assay and Western (immuno-) blot analysis [20].
• To avoid rosette formation (aggregation), which would preclude crystallization, this hydrophobic tail was removed from a membrane-free form of HN by proteolytic digestion [20].

References