{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:10:15Z","timestamp":1787238615638,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,22]],"date-time":"2018-12-22T00:00:00Z","timestamp":1545436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Three neuraminidase inhibitors (NAIs: Oseltamivir, zanamivir and peramivir) are currently approved in many countries for the treatment of influenza A and B infections. The emergence of influenza B viruses (IBVs) containing mutations of cross-resistance to these NAIs constitutes a serious clinical threat. Herein, we used a reverse genetics system for the current B\/Phuket\/3073\/2013 vaccine strain to investigate the impact on in vitro properties and virulence of H136N, R152K, D198E\/N, I222T and N294S NA substitutions (N2 numbering), reported by the World Health Organization (WHO) as clinical markers of reduced or highly-reduced inhibition (RI\/HRI) to multiple NAIs. Recombinant viruses were tested by NA inhibition assays. Their replicative capacity and virulence were evaluated in ST6GalI-MDCK cells and BALB\/c mice, respectively. All NA mutants (excepted D198E\/N) showed RI\/HRI phenotypes against \u2265 2 NAIs. These mutants grew to comparable titers of the recombinant wild-type (WT) IBV in vitro, and some of them (H136N, I222T and N294S mutants) induced more weight loss and mortality in BALB\/c mice in comparison to the recombinant WT IBV. These results demonstrate that, in contemporary IBVs, some NA mutations may confer RI\/HRI phenotypes to existing NAIs without altering the viral fitness. This reinforces the need for development of novel antiviral strategies with different mechanisms of action.<\/jats:p>","DOI":"10.3390\/v11010006","type":"journal-article","created":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T10:37:49Z","timestamp":1545647869000},"page":"6","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Vitro Properties and Virulence of Contemporary Recombinant Influenza B Viruses Harboring Mutations of Cross-Resistance to Neuraminidase Inhibitors"],"prefix":"10.3390","volume":"11","author":[{"given":"Cl\u00e9ment","family":"Fage","sequence":"first","affiliation":[{"name":"Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, 2705 Boulevard Laurier, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yacine","family":"Abed","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, 2705 Boulevard Laurier, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liva","family":"Checkmahomed","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, 2705 Boulevard Laurier, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Venable","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, 2705 Boulevard Laurier, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Boivin","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, 2705 Boulevard Laurier, Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.2002.1719","article-title":"Reappearance and global spread of variants of influenza B\/victoria\/2\/87 lineage viruses in the 2000\u20132001 and 2001\u20132002 seasons","volume":"303","author":"Shaw","year":"2002","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4818","DOI":"10.1128\/JVI.00059-15","article-title":"Domestic pigs are susceptible to infection with influenza B viruses","volume":"89","author":"Ran","year":"2015","journal-title":"J. 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