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Virology. 2018 Sep;522:122-130. doi: 10.1016/j.virol.2018.07.002. Epub 2018 Jul 18.

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

Author information

1
Infectious Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, IP, Av. Padre Cruz, 1649-016 Lisbon, Portugal; Host-Pathogen Interaction Unit, Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisbon, Portugal. Electronic address: vanessa.correia@insa-min-saude.pt.
2
Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Rua da Junqueira 100, 1349-008 Lisbon, Portugal. Electronic address: ana.abecasis@ihmt.unl.pt.
3
Infectious Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, IP, Av. Padre Cruz, 1649-016 Lisbon, Portugal; Host-Pathogen Interaction Unit, Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisbon, Portugal. Electronic address: h.rebelo.andrade@insa.min-saude.pt.

Abstract

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.

KEYWORDS:

Influenza; Neuraminidase; Overall selection; Positively selected sites; Site-specific selective pressures; dN/dS ratio

PMID:
30029011
DOI:
10.1016/j.virol.2018.07.002
[Indexed for MEDLINE]

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