title: Full Genome Characterization of Human Influenza A/H3N2 Isolates from Asian Countries Reveals a Rare Amantadine Resistance-Conferring Mutation and Novel PB1-F2 Polymorphisms.
abstract: Influenza A viruses evolve at a high rate requiring continuous monitoring to maintain the efficacy of vaccines and antiviral drugs. We performed next generation sequencing analysis of 100 influenza A/H3N2 isolates collected in four Asian countries (Japan, Lebanon, Myanmar, and Vietnam) during 2012-2015. Phylogenetic analysis revealed several reassortment events leading to the circulation of multiple clades within the same season. This was particularly evident during the 2013 and 2013/2014 seasons. Importantly, our data showed that certain lineages appeared to be fitter and were able to persist into the following season. The majority of A/H3N2 viruses continued to harbor the M2-S31N mutation conferring amantadine-resistance. In addition, an S31D mutation in the M2-protein, conferring a similar level of resistance as the S31N mutation, was detected in three isolates obtained in Japan during the 2014/2015 season. None of the isolates possessed the NA-H274Y mutation conferring oseltamivir-resistance, though a few isolates were found to contain mutations at the catalytic residue 151 (D151A/G/N or V) of the NA protein. These variations did not alter the susceptibility to neuraminidase inhibitors and were not detected in the original clinical specimens, suggesting that they had been acquired during their passage in MDCK cells. Novel polymorphisms were detected in the PB1-F2 open-reading frame resulting in truncations in the protein of 24-34 aminoacids in length. Thus, this study has demonstrated the utility of monitoring the full genome of influenza viruses to allow the detection of the potentially fittest lineages. This enhances our ability to predict the strain(s) most likely to persist into the following seasons and predict the potential degree of vaccine match or mismatch with the seasonal influenza season for that year. This will enable the public health and clinical teams to prepare for any related healthcare burden, depending on whether the vaccine match is predicted to be good or poor for that season.
authors.affiliation: Department of Pathology, Immunology, and Microbiology, Faculty of Medicine American University of BeirutBeirut, Lebanon; Center for Infectious Disease Research, Faculty of Medicine American University of BeirutBeirut, Lebanon.
authors.forename: Hassan
authors.initials: H
authors.lastname: Zaraket
authors.affiliation: Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University Niigata, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University Niigata, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hibino
authors.affiliation: Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University Niigata, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Yagami
authors.affiliation: Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Odagiri
authors.affiliation: Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization Ibaraki, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Takemae
authors.affiliation: Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization Ibaraki, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tsunekuni
authors.affiliation: Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization Ibaraki, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Traditional Medicine Nay Pyi Taw, Myanmar.
authors.forename: Yi Yi
authors.initials: YY
authors.lastname: Myint
authors.affiliation: Sanpya Hospital Yangon, Myanmar.
authors.forename: Yadanar
authors.initials: Y
authors.lastname: Kyaw
authors.affiliation: National Health Laboratory Yangon, Myanmar.
authors.forename: Khin Yi
authors.initials: KY
authors.lastname: Oo
authors.affiliation: National Health Laboratory Yangon, Myanmar.
authors.forename: Htay Htay
authors.initials: HH
authors.lastname: Tin
authors.affiliation: Pyinmana Township Hospital Nay Pyi Taw, Myanmar.
authors.forename: Nay
authors.initials: N
authors.lastname: Lin
authors.affiliation: National Institute of Hygiene and Epidemiology Hanoi, Vietnam.
authors.forename: Nguyen Phuong
authors.initials: NP
authors.lastname: Anh
authors.affiliation: National Institute of Hygiene and Epidemiology Hanoi, Vietnam.
authors.forename: Nguyen Le Khanh
authors.initials: Nle K
authors.lastname: Hang
authors.affiliation: National Institute of Hygiene and Epidemiology Hanoi, Vietnam.
authors.forename: Le Quynh
authors.initials: le Q
authors.lastname: Mai
authors.affiliation: Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata UniversityNiigata, Japan; Department of Community Health, Faculty of Medicine, UKM Medical CentreKuala Lumpur, Malaysia.
authors.forename: Mohd R
authors.initials: MR
authors.lastname: Hassan
authors.affiliation: Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University Niigata, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Shobugawa
authors.affiliation: Clinical Microbiology, University Hospitals LeicesterLeicester, UK; Department of Infection, Immunity and Inflammation, University of LeicesterLeceister, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Tang
authors.affiliation: Center for Infectious Disease Research, Faculty of Medicine American University of BeirutBeirut, Lebanon; Division of Pediatric Infectious Diseases, Department of Pediatrics and Adolescent Medicine and the Center for Infectious Diseases Research, American University of Beirut Medical CenterBeirut, Lebanon.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Dbaibo
authors.affiliation: Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University Niigata, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Saito
keywords: PB1-F2; antiviral; evolution; full-genome; influenza A/H3N2; phylogenetic analysis; reassortment; vaccine