Compensatory evolution of net-charge in influenza A virus hemagglutinin.
The propagation of influenza A virus depends on the balance between the activities of hemagglutinin (HA) for binding to host cells and neuraminidase (NA) for releasing from infected cells (HA-NA balance). Since the host cell membrane and the sialic acid receptor are negatively charged, the amino aci...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3395715?pdf=render |
| _version_ | 1818509880880791552 |
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| author | Yuki Kobayashi Yoshiyuki Suzuki |
| author_facet | Yuki Kobayashi Yoshiyuki Suzuki |
| author_sort | Yuki Kobayashi |
| collection | DOAJ |
| description | The propagation of influenza A virus depends on the balance between the activities of hemagglutinin (HA) for binding to host cells and neuraminidase (NA) for releasing from infected cells (HA-NA balance). Since the host cell membrane and the sialic acid receptor are negatively charged, the amino acid substitutions increasing (charge+) and decreasing (charge-) the positive charge of HA subunit 1 (HA1) enhance and reduce, respectively, the binding avidity and affinity. The positive charge of HA1 in human influenza A virus bearing subtype H3N2 (A/H3N2 virus) was observed to have increased during evolution, but the evolutionary mechanism for this observation was unclear because this may disrupt the HA-NA balance. Here we show, from the phylogenetic analysis of HA for human A/H3N2 and A/H1N1 viruses, that the relative frequencies of charge+ and charge- substitutions were elevated on the branches where the number of N-glycosylation sites (NGS) increased and decreased, respectively, compared to those where the number of NGS did not change. On the latter branches, the net-charge of HA1 appeared to have been largely maintained to preserve its structure and function. Since the charge+ and charge- substitutions in HA1 have opposite effects to the gain and loss of NGS on the binding and release of the virus, the net-charge of HA1 may have evolved to compensate for the effect of the gain and loss of NGS, probably through changing the avidity. Apparently, the relative frequency of charge- substitutions in HA1 of A/H3N2 virus was elevated after the introduction of oseltamivir, and that of charge+ substitutions in HA1 of A/H1N1 virus was elevated after the spread of oseltamivir resistance. These observations may also be explained by the compensatory effect of the net-charge in HA1 on the NA activity for keeping the HA-NA balance. |
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| format | Article |
| id | doaj.art-53bc50fab4454504a900e34e42ce3246 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T22:51:28Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-53bc50fab4454504a900e34e42ce32462022-12-22T01:30:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4042210.1371/journal.pone.0040422Compensatory evolution of net-charge in influenza A virus hemagglutinin.Yuki KobayashiYoshiyuki SuzukiThe propagation of influenza A virus depends on the balance between the activities of hemagglutinin (HA) for binding to host cells and neuraminidase (NA) for releasing from infected cells (HA-NA balance). Since the host cell membrane and the sialic acid receptor are negatively charged, the amino acid substitutions increasing (charge+) and decreasing (charge-) the positive charge of HA subunit 1 (HA1) enhance and reduce, respectively, the binding avidity and affinity. The positive charge of HA1 in human influenza A virus bearing subtype H3N2 (A/H3N2 virus) was observed to have increased during evolution, but the evolutionary mechanism for this observation was unclear because this may disrupt the HA-NA balance. Here we show, from the phylogenetic analysis of HA for human A/H3N2 and A/H1N1 viruses, that the relative frequencies of charge+ and charge- substitutions were elevated on the branches where the number of N-glycosylation sites (NGS) increased and decreased, respectively, compared to those where the number of NGS did not change. On the latter branches, the net-charge of HA1 appeared to have been largely maintained to preserve its structure and function. Since the charge+ and charge- substitutions in HA1 have opposite effects to the gain and loss of NGS on the binding and release of the virus, the net-charge of HA1 may have evolved to compensate for the effect of the gain and loss of NGS, probably through changing the avidity. Apparently, the relative frequency of charge- substitutions in HA1 of A/H3N2 virus was elevated after the introduction of oseltamivir, and that of charge+ substitutions in HA1 of A/H1N1 virus was elevated after the spread of oseltamivir resistance. These observations may also be explained by the compensatory effect of the net-charge in HA1 on the NA activity for keeping the HA-NA balance.http://europepmc.org/articles/PMC3395715?pdf=render |
| spellingShingle | Yuki Kobayashi Yoshiyuki Suzuki Compensatory evolution of net-charge in influenza A virus hemagglutinin. PLoS ONE |
| title | Compensatory evolution of net-charge in influenza A virus hemagglutinin. |
| title_full | Compensatory evolution of net-charge in influenza A virus hemagglutinin. |
| title_fullStr | Compensatory evolution of net-charge in influenza A virus hemagglutinin. |
| title_full_unstemmed | Compensatory evolution of net-charge in influenza A virus hemagglutinin. |
| title_short | Compensatory evolution of net-charge in influenza A virus hemagglutinin. |
| title_sort | compensatory evolution of net charge in influenza a virus hemagglutinin |
| url | http://europepmc.org/articles/PMC3395715?pdf=render |
| work_keys_str_mv | AT yukikobayashi compensatoryevolutionofnetchargeininfluenzaavirushemagglutinin AT yoshiyukisuzuki compensatoryevolutionofnetchargeininfluenzaavirushemagglutinin |