Molecular footprints of selective pressure in the neuraminidase gene of currently circulating human influenza subtypes and lineages

Detalhes bibliográficos
Autor(a) principal: Correia, Vanessa
Data de Publicação: 2018
Outros Autores: Abecasis, Ana B., Rebelo-de-Andrade, Helena
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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spelling 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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