Hemagglutinin-neuraminidase (HN) amino acid alterations in neutralization escape mutants of Kilham mumps virus

Kövamees, Jan; Rydbeck, Robert; Örvell, Claes; Norrby, Erling

doi:10.1016/0168-1702(90)90073-k

Cited by 63 publications

(46 citation statements)

References 30 publications

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“…Recently, Xing et al (1991) have also reported a minimum epitope sequence of 5 residues for three monoclonal anti-mucine antibodies (BCl , BC2, and BC3), and the number of critical residues found was 4 for BCl and BC2, and 1 for BC3. In addition, the epitope length reported for other monoclonal antibodies falls into the range of 5-10 residues (Anderson et al, 1988;Kovamees et al, 1990;Scott et al, 1990), and the minimum sequence found is between 5 and 7 residues (Anderson et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Antigen‐antibody interactions: Elucidation of the epitope and strain‐specificity of a monoclonal antibody directed against the pilin protein adherence binding domain of Pseudomonas aeruginosa strain K

et al. 1992

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The C-terminal region of Pseudomonas aeruginosa strain K (PAK) pilin comprises both an epitope for the strainspecific monoclonal antibody PK99H, which blocks pilus-mediated adherence, and the adherence binding domain for buccal and tracheal epithelial cells. The PK99H epitope was located in sequence 134-140 (Asp-Glu-Gln-PheIle-Pro-Lys) by using a single alanine replacement analysis on the 17-residue synthetic peptide corresponding to the PAK C-terminal sequence 128-144. Indeed, a 7-residue peptide corresponding to this sequence was shown to have a similar binding affinity to that of the native conformationally constrained (disulfide bridged) 17-residue peptide. This epitope was found to contain two critical residues (PheI3' and LysI4O) and one nonessential residue ( G l r~'~~) .Interestingly, the peptide, Phe-Ile-Pro-Lys, which constitutes the four most important side chains for antibody binding did not bind to PK99H. It was of interest to investigate the structural basis of the strainspecificity of PK99H utilizing naturally occurring pilin sequences. Therefore, all different residues found in the sequence corresponding to the PK99H epitope of the four other strains (PAO, CD4, K122-4, and KB7) were substituted one at a time in the PAK sequence and the changes in binding affinity of these analogs to the antibody PK99H were determined by competitive ELISA. The strain-specificity of PK99H for strains PAO, K122-4, and KB7 can be explained by the accumulated sequence changes in these strains, and at least two amino acid changes were required to explain the strain-specificity of PK99H. Similarly, cross-reactivity of PK99H with CD4 can be explained by the fact that there was only one side chain responsible for decreasing binding affinity compared to the PAK sequence.

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Section: Discussionmentioning

confidence: 99%

Antigen‐antibody interactions: Elucidation of the epitope and strain‐specificity of a monoclonal antibody directed against the pilin protein adherence binding domain of Pseudomonas aeruginosa strain K

et al. 1992

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“…Single amino acid changes in the envelope proteins of several viruses, including mumps virus (18) and MV (20), were found to have a profound and differential influence on pathogenesis. Alteration of viral envelope proteins may have a variety of pathogenic consequences: single mutations affect neuroinvasiveness of tick-borne encephalitis virus (14,33,41), neurovirulence of dengue virus (13) and Japanese encephalitis virus (28), viral persistence in the case of lymphocytic choriomeningitis virus (25), cell-to-cell spread of rabies virus (6,40), and virus replication efficiency of Sindbis virus (8).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Measles Viruses Expressing Altered Hemagglutinin (H) Genes: Functional Separation of Mutations Determining H Antibody Escape from Neurovirulence

Moeller

Duprex

et al. 2001

J Virol

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Measles virus (MV) strain CAM/RB, which was adapted to growth in the brain of newborn rodents, is highly neurovirulent. It has been reported earlier that experimentally selected virus variants escaping from the monoclonal antibodies (MAbs) Nc32 and L77 to hemagglutinin (H) preserved their neurovirulence, whereas mutants escaping MAbs K71 and K29 were found to be strongly attenuated (U. G. Liebert et al., J. Virol. 68:1486-1493, 1994). To investigate the molecular basis of these findings, we have generated a panel of recombinant MVs expressing the H protein from CAM/RB and introduced the amino acid substitutions thought to be responsible for antibody escape and/or neurovirulence. Using these recombinant viruses, we identified the amino acid changes conferring escape from the MAbs L77 (377R3Q and 378M3K), Nc32 (388G3S), K71 (492E3K and 550S3P), and K29 (535E3G). When the corresponding recombinant viruses were tested in brains of newborn rodents, we found that the mutations mediating antibody escape did not confer differential neurovirulence. In contrast, however, replacement of two different amino acids, at positions 195G3R and 200S3N, which had been described for the escape mutant set, caused the change in neurovirulence. Thus, antibody escape and neurovirulence appear not to be associated with the same structural alterations of the MV H protein.

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“…When mapped on the structure of MuV-HN, the great majority of the reported epitopes of antiMuV-HN Abs (8,26,27) are located around α-helices A (positions 264-269), B (positions 331-336), and C (positions 354-365) of the MuV-HN head domain (Fig. S7).…”

Section: Discussionmentioning

confidence: 99%

Trisaccharide containing α2,3-linked sialic acid is a receptor for mumps virus

Kubota

Takeuchi

Watanabe

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mumps virus (MuV) remains an important pathogen worldwide, causing epidemic parotitis, orchitis, meningitis, and encephalitis. Here we show that MuV preferentially uses a trisaccharide containing α2,3-linked sialic acid in unbranched sugar chains as a receptor. Crystal structures of the MuV attachment protein hemagglutinin-neuraminidase (MuV-HN) alone and in complex with the α2,3-sialylated trisaccharide revealed that in addition to the interaction between the MuV-HN active site residues and sialic acid, other residues, including an aromatic residue, stabilize the third sugar of the trisaccharide. The importance of the aromatic residue and the third sugar in the MuV-HN−receptor interaction was confirmed by computational energy calculations, isothermal titration calorimetry studies, and glycan-binding assays. Furthermore, MuV-HN was found to bind more efficiently to unbranched α2,3-sialylated sugar chains compared with branched ones. Importantly, the strategically located aromatic residue is conserved among the HN proteins of sialic acid-using paramyxoviruses, and alanine substitution compromised their ability to support cellcell fusion. These results suggest that not only the terminal sialic acid but also the adjacent sugar moiety contribute to receptor function for mumps and these paramyxoviruses. The distribution of structurally different sialylated glycans in tissues and organs may explain in part MuV's distinct tropism to glandular tissues and the central nervous system. In the crystal structure, the epitopes for neutralizing antibodies are located around the α-helices of MuV-HN that are not well conserved in amino acid sequences among different genotypes of MuV. This may explain the fact that MuV reinfection sometimes occurs. structure | entry | receptor | infection | paramyxovirus

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Hemagglutinin-neuraminidase (HN) amino acid alterations in neutralization escape mutants of Kilham mumps virus

Cited by 63 publications

References 30 publications

Antigen‐antibody interactions: Elucidation of the epitope and strain‐specificity of a monoclonal antibody directed against the pilin protein adherence binding domain of Pseudomonas aeruginosa strain K

Antigen‐antibody interactions: Elucidation of the epitope and strain‐specificity of a monoclonal antibody directed against the pilin protein adherence binding domain of Pseudomonas aeruginosa strain K

Recombinant Measles Viruses Expressing Altered Hemagglutinin (H) Genes: Functional Separation of Mutations Determining H Antibody Escape from Neurovirulence

Trisaccharide containing α2,3-linked sialic acid is a receptor for mumps virus

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