Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/6324 |
Resumo: | Influenza neuraminidase (NA) is under selective pressure (SP) of both host immune system and drug use. Here, we assembled large datasets of NA sequences of worldwide circulating viruses to estimate the global and site-specific SP acting on all current subtypes/lineages of human influenza NA. An overall negative SP of similar magnitude and a prevalence of negatively selected sites were observed for all subtypes/lineages. Positively selected sites varied according to the subtype/lineage, including N1-NA sites 247 and 275, N2-NA sites 148 and 151, and B/Victoria-NA site 395 associated with drug-resistance or reduced susceptibility. These results evidenced a potential role of positive selection in the low-level spread of A(H1N1)pdm09-H275Y drug-resistant viruses, and alerted for a potential higher risk of spread of a synergistic A(H1N1)pdm09 drug-resistant variant (H275Y/S247N). The positive selection detected at N2-NA sites 148 and 151 was probably an artefact from cell-culture. Overall mapping revealed six potential new druggable regions. |
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Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineagesGenotypeGlobal HealthHumansInfluenza A virusInfluenza B virusInfluenza, HumanNeuraminidaseSequence Analysis, DNAViral ProteinsSelection, GeneticInfecções RespiratóriasInfluenza neuraminidase (NA) is under selective pressure (SP) of both host immune system and drug use. Here, we assembled large datasets of NA sequences of worldwide circulating viruses to estimate the global and site-specific SP acting on all current subtypes/lineages of human influenza NA. An overall negative SP of similar magnitude and a prevalence of negatively selected sites were observed for all subtypes/lineages. Positively selected sites varied according to the subtype/lineage, including N1-NA sites 247 and 275, N2-NA sites 148 and 151, and B/Victoria-NA site 395 associated with drug-resistance or reduced susceptibility. These results evidenced a potential role of positive selection in the low-level spread of A(H1N1)pdm09-H275Y drug-resistant viruses, and alerted for a potential higher risk of spread of a synergistic A(H1N1)pdm09 drug-resistant variant (H275Y/S247N). The positive selection detected at N2-NA sites 148 and 151 was probably an artefact from cell-culture. Overall mapping revealed six potential new druggable regions.V. Correia was funded by a Ph.D. Studentship from Fundação para a Ciência e Tecnologia (FCT), Portugal (SFRH/BD/48532/2008), and by a research grant from Fundacão Calouste Gulbenkian, Portugal (Project SDH49). A.B. Abecasis was funded by a postdoctoral fellowship from FCT (SFRH/BPD/65605/2009) and by an Investigator FCT Starting Researcher Contract.Elsevier/ Academic PressRepositório Científico do Instituto Nacional de SaúdeCorreia, VanessaAbecasis, Ana B.Rebelo-de-Andrade, Helena2019-03-27T11:25:11Z2018-092018-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6324engVirology. 2018 Sep;522:122-130. doi: 10.1016/j.virol.2018.07.002. Epub 2018 Jul 180042-682210.1016/j.virol.2018.07.002info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:21Zoai:repositorio.insa.pt:10400.18/6324Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:40:58.418882Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages |
title |
Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages |
spellingShingle |
Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages Correia, Vanessa Genotype Global Health Humans Influenza A virus Influenza B virus Influenza, Human Neuraminidase Sequence Analysis, DNA Viral Proteins Selection, Genetic Infecções Respiratórias |
title_short |
Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages |
title_full |
Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages |
title_fullStr |
Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages |
title_full_unstemmed |
Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages |
title_sort |
Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages |
author |
Correia, Vanessa |
author_facet |
Correia, Vanessa Abecasis, Ana B. Rebelo-de-Andrade, Helena |
author_role |
author |
author2 |
Abecasis, Ana B. Rebelo-de-Andrade, Helena |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Correia, Vanessa Abecasis, Ana B. Rebelo-de-Andrade, Helena |
dc.subject.por.fl_str_mv |
Genotype Global Health Humans Influenza A virus Influenza B virus Influenza, Human Neuraminidase Sequence Analysis, DNA Viral Proteins Selection, Genetic Infecções Respiratórias |
topic |
Genotype Global Health Humans Influenza A virus Influenza B virus Influenza, Human Neuraminidase Sequence Analysis, DNA Viral Proteins Selection, Genetic Infecções Respiratórias |
description |
Influenza neuraminidase (NA) is under selective pressure (SP) of both host immune system and drug use. Here, we assembled large datasets of NA sequences of worldwide circulating viruses to estimate the global and site-specific SP acting on all current subtypes/lineages of human influenza NA. An overall negative SP of similar magnitude and a prevalence of negatively selected sites were observed for all subtypes/lineages. Positively selected sites varied according to the subtype/lineage, including N1-NA sites 247 and 275, N2-NA sites 148 and 151, and B/Victoria-NA site 395 associated with drug-resistance or reduced susceptibility. These results evidenced a potential role of positive selection in the low-level spread of A(H1N1)pdm09-H275Y drug-resistant viruses, and alerted for a potential higher risk of spread of a synergistic A(H1N1)pdm09 drug-resistant variant (H275Y/S247N). The positive selection detected at N2-NA sites 148 and 151 was probably an artefact from cell-culture. Overall mapping revealed six potential new druggable regions. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-09 2018-09-01T00:00:00Z 2019-03-27T11:25:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/6324 |
url |
http://hdl.handle.net/10400.18/6324 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Virology. 2018 Sep;522:122-130. doi: 10.1016/j.virol.2018.07.002. Epub 2018 Jul 18 0042-6822 10.1016/j.virol.2018.07.002 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier/ Academic Press |
publisher.none.fl_str_mv |
Elsevier/ Academic Press |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1817552959491276800 |