Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase
Monoclonal antibodies which inhibit influenza virus neuraminidase (NA) and which therefore indirectly neutralize virus infectivity bind to epitopes located on the rim of the active-site crater. The three-dimensional structure of one of these epitopes, recognized by monoclonal antibody NC41, has prev...
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crasmicro:10.1128/jvi.64.12.5797-5803.1990 2024-09-15T18:32:34+00:00 Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase Air, G M Laver, W G Webster, R G 1990 http://dx.doi.org/10.1128/jvi.64.12.5797-5803.1990 https://journals.asm.org/doi/pdf/10.1128/jvi.64.12.5797-5803.1990 en eng American Society for Microbiology https://journals.asm.org/non-commercial-tdm-license Journal of Virology volume 64, issue 12, page 5797-5803 ISSN 0022-538X 1098-5514 journal-article 1990 crasmicro https://doi.org/10.1128/jvi.64.12.5797-5803.1990 2024-07-15T04:09:16Z Monoclonal antibodies which inhibit influenza virus neuraminidase (NA) and which therefore indirectly neutralize virus infectivity bind to epitopes located on the rim of the active-site crater. The three-dimensional structure of one of these epitopes, recognized by monoclonal antibody NC41, has previously been determined (W. R. Tulip, J. N. Varghese, R. G. Webster, G. M. Air, W. G. Laver, and P. M. Colman, Cold Spring Harbor Symp. Quant. Biol. 54:257-263, 1989). Nineteen escape mutants of influenza virus A/tern/Australia/G70c/75 (N9) NA selected with NC41 were sequenced. A surprising restriction was seen in the sequence changes involved. Ten mutants had a Ser-to-Phe change at amino acid 372, and six others had mutations at position 367. No escape mutants with changes at 369 or 370 were found, although these mutations were selected with other antibodies and rendered the epitope unrecognizable by antibody NC41. Another N9 NA, from A/ruddy turnstone/NJ/85, which differs by 14 amino acids from the tern virus NA, still bound antibody NC41. Epitope mapping by selecting multiple escape mutants with antibody NC41 thus identified only three of the five polypeptide loops on NA that contact the antibody. Escape mutants selected sequentially with three different monoclonal antibodies showed three sequence changes in two loops of the NC41 epitope. The multiple mutants were indistinguishable from wild-type virus by using polyclonal rabbit antiserum in double immunodiffusion tests, but NA inhibition titers were fourfold lower. The results suggest that although the NC41 epitope contains 22 amino acids, only a few of these are so critical to the interaction with antibody that a single sequence change allows selection of an escape mutant. In that case, the variety of amino acid sequence changes which can lead to polyclonal selection of new epidemic viruses during antigenic drift might be very limited. Article in Journal/Newspaper Ruddy Turnstone ASM Journals (American Society for Microbiology) Journal of Virology 64 12 5797 5803 |
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English |
description |
Monoclonal antibodies which inhibit influenza virus neuraminidase (NA) and which therefore indirectly neutralize virus infectivity bind to epitopes located on the rim of the active-site crater. The three-dimensional structure of one of these epitopes, recognized by monoclonal antibody NC41, has previously been determined (W. R. Tulip, J. N. Varghese, R. G. Webster, G. M. Air, W. G. Laver, and P. M. Colman, Cold Spring Harbor Symp. Quant. Biol. 54:257-263, 1989). Nineteen escape mutants of influenza virus A/tern/Australia/G70c/75 (N9) NA selected with NC41 were sequenced. A surprising restriction was seen in the sequence changes involved. Ten mutants had a Ser-to-Phe change at amino acid 372, and six others had mutations at position 367. No escape mutants with changes at 369 or 370 were found, although these mutations were selected with other antibodies and rendered the epitope unrecognizable by antibody NC41. Another N9 NA, from A/ruddy turnstone/NJ/85, which differs by 14 amino acids from the tern virus NA, still bound antibody NC41. Epitope mapping by selecting multiple escape mutants with antibody NC41 thus identified only three of the five polypeptide loops on NA that contact the antibody. Escape mutants selected sequentially with three different monoclonal antibodies showed three sequence changes in two loops of the NC41 epitope. The multiple mutants were indistinguishable from wild-type virus by using polyclonal rabbit antiserum in double immunodiffusion tests, but NA inhibition titers were fourfold lower. The results suggest that although the NC41 epitope contains 22 amino acids, only a few of these are so critical to the interaction with antibody that a single sequence change allows selection of an escape mutant. In that case, the variety of amino acid sequence changes which can lead to polyclonal selection of new epidemic viruses during antigenic drift might be very limited. |
format |
Article in Journal/Newspaper |
author |
Air, G M Laver, W G Webster, R G |
spellingShingle |
Air, G M Laver, W G Webster, R G Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase |
author_facet |
Air, G M Laver, W G Webster, R G |
author_sort |
Air, G M |
title |
Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase |
title_short |
Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase |
title_full |
Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase |
title_fullStr |
Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase |
title_full_unstemmed |
Mechanism of antigenic variation in an individual epitope on influenza virus N9 neuraminidase |
title_sort |
mechanism of antigenic variation in an individual epitope on influenza virus n9 neuraminidase |
publisher |
American Society for Microbiology |
publishDate |
1990 |
url |
http://dx.doi.org/10.1128/jvi.64.12.5797-5803.1990 https://journals.asm.org/doi/pdf/10.1128/jvi.64.12.5797-5803.1990 |
genre |
Ruddy Turnstone |
genre_facet |
Ruddy Turnstone |
op_source |
Journal of Virology volume 64, issue 12, page 5797-5803 ISSN 0022-538X 1098-5514 |
op_rights |
https://journals.asm.org/non-commercial-tdm-license |
op_doi |
https://doi.org/10.1128/jvi.64.12.5797-5803.1990 |
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Journal of Virology |
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64 |
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12 |
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5797 |
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5803 |
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