Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model
Characterization of a pandemic 2009 H1N1 influenza virus isolated from a fatal case patient (F-IAV), showed the presence of three different mutations; potential determinants of its high pathogenicity that were located in the polymerase subunits (PB2 A221T and PA D529N) and the hemagglutinin (HA S110...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00132/full |
| _version_ | 1819044972426428416 |
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| author | Amelia Nieto Amelia Nieto Jasmina Vasilijevic Nuno Brito Santos Noelia Zamarreño Noelia Zamarreño Pablo López Maria Joao Amorim Ana Falcon Ana Falcon |
| author_facet | Amelia Nieto Amelia Nieto Jasmina Vasilijevic Nuno Brito Santos Noelia Zamarreño Noelia Zamarreño Pablo López Maria Joao Amorim Ana Falcon Ana Falcon |
| author_sort | Amelia Nieto |
| collection | DOAJ |
| description | Characterization of a pandemic 2009 H1N1 influenza virus isolated from a fatal case patient (F-IAV), showed the presence of three different mutations; potential determinants of its high pathogenicity that were located in the polymerase subunits (PB2 A221T and PA D529N) and the hemagglutinin (HA S110L). Recombinant viruses containing individually or in combination the polymerase mutations in the backbone of A/California/04/09 (CAL) showed that PA D529N was clearly involved in the increased pathogenicity of the F-IAV virus. Here, we have evaluated the contribution of HA S110L to F-IAV pathogenicity, through introduction of this point mutation in CAL recombinant virus (HA mut). The HA S110L protein has similar pH stability, comparable mobility, and entry properties both in human and mouse cultured cells that wild type HA. The change HA S110L leads to a non-significant trend to reduce the replication capacity of influenza virus in tissue culture, and HA mut is better neutralized than CAL virus by monoclonal and polyclonal antibodies against HA from CAL strain. In addition, recombinant viruses containing HA S110L alone or in combination with polymerase mutations considerably increased the LD50 in infected mice. Characterization of the lungs of HA mut infected animals showed reduced lung damage and inflammation compared with CAL infected mice. Accordingly, lower virus replication, decreased presence in bronchioli and parenchyma and lower leukocytes and epithelial infected cells were found in the lungs of HA mut-infected animals. Our results indicate that, mutation HA S110L constitutes a determinant of attenuation and suggest that its interaction with components of the respiratory tract mucus and lectins, that play an important role on influenza virus outcome, may constitute a physical barrier impeding the infection of the target cells, thus compromising the infection outcome. |
| first_indexed | 2024-12-21T10:21:10Z |
| format | Article |
| id | doaj.art-59a175c45434481f80c9983255e3c793 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T10:21:10Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-59a175c45434481f80c9983255e3c7932022-12-21T19:07:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-02-011010.3389/fimmu.2019.00132414246Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse ModelAmelia Nieto0Amelia Nieto1Jasmina Vasilijevic2Nuno Brito Santos3Noelia Zamarreño4Noelia Zamarreño5Pablo López6Maria Joao Amorim7Ana Falcon8Ana Falcon9National Center for Biotechnology (CNB-CSIC), Madrid, SpainCenter for Biomedical Research (CIBER), Madrid, SpainNational Center for Biotechnology (CNB-CSIC), Madrid, SpainCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, PortugalNational Center for Biotechnology (CNB-CSIC), Madrid, SpainCenter for Biomedical Research (CIBER), Madrid, SpainNational Center for Biotechnology (CNB-CSIC), Madrid, SpainCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência, Oeiras, PortugalNational Center for Biotechnology (CNB-CSIC), Madrid, SpainCenter for Biomedical Research (CIBER), Madrid, SpainCharacterization of a pandemic 2009 H1N1 influenza virus isolated from a fatal case patient (F-IAV), showed the presence of three different mutations; potential determinants of its high pathogenicity that were located in the polymerase subunits (PB2 A221T and PA D529N) and the hemagglutinin (HA S110L). Recombinant viruses containing individually or in combination the polymerase mutations in the backbone of A/California/04/09 (CAL) showed that PA D529N was clearly involved in the increased pathogenicity of the F-IAV virus. Here, we have evaluated the contribution of HA S110L to F-IAV pathogenicity, through introduction of this point mutation in CAL recombinant virus (HA mut). The HA S110L protein has similar pH stability, comparable mobility, and entry properties both in human and mouse cultured cells that wild type HA. The change HA S110L leads to a non-significant trend to reduce the replication capacity of influenza virus in tissue culture, and HA mut is better neutralized than CAL virus by monoclonal and polyclonal antibodies against HA from CAL strain. In addition, recombinant viruses containing HA S110L alone or in combination with polymerase mutations considerably increased the LD50 in infected mice. Characterization of the lungs of HA mut infected animals showed reduced lung damage and inflammation compared with CAL infected mice. Accordingly, lower virus replication, decreased presence in bronchioli and parenchyma and lower leukocytes and epithelial infected cells were found in the lungs of HA mut-infected animals. Our results indicate that, mutation HA S110L constitutes a determinant of attenuation and suggest that its interaction with components of the respiratory tract mucus and lectins, that play an important role on influenza virus outcome, may constitute a physical barrier impeding the infection of the target cells, thus compromising the infection outcome.https://www.frontiersin.org/article/10.3389/fimmu.2019.00132/fullinfluenza virusHA S110L mutationattenuationin vivo pathogenicityviral entry |
| spellingShingle | Amelia Nieto Amelia Nieto Jasmina Vasilijevic Nuno Brito Santos Noelia Zamarreño Noelia Zamarreño Pablo López Maria Joao Amorim Ana Falcon Ana Falcon Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model Frontiers in Immunology influenza virus HA S110L mutation attenuation in vivo pathogenicity viral entry |
| title | Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model |
| title_full | Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model |
| title_fullStr | Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model |
| title_full_unstemmed | Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model |
| title_short | Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model |
| title_sort | mutation s110l of h1n1 influenza virus hemagglutinin a potent determinant of attenuation in the mouse model |
| topic | influenza virus HA S110L mutation attenuation in vivo pathogenicity viral entry |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00132/full |
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