Full genome characterization of human influenza A/H3N2 isolates from asian countries reveals a rare amantadine resistance-conferring mutation and novel PB1-F2 polymorphisms

Japanese Influenza Collaborative Study Group

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Article number262
JournalFrontiers in Microbiology
Volume7
Issue numberMAR
DOIs
Publication statusPublished - 7 Mar 2016
Externally publishedYes

Fingerprint

Amantadine
Human Influenza
Genome
Mutation
Vaccines
Japan
H3N2 Subtype Influenza A Virus
Myanmar
Lebanon
Oseltamivir
Proteins
Madin Darby Canine Kidney Cells
Vietnam
Influenza A virus
Neuraminidase
Orthomyxoviridae
Open Reading Frames
Antiviral Agents
Public Health
Delivery of Health Care

Keywords

  • Antiviral
  • Evolution
  • Full-genome
  • Influenza A/H3N2
  • PB1-F2
  • Phylogenetic analysis
  • Reassortment
  • Vaccine

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Full genome characterization of human influenza A/H3N2 isolates from asian countries reveals a rare amantadine resistance-conferring mutation and novel PB1-F2 polymorphisms. / Japanese Influenza Collaborative Study Group.

In: Frontiers in Microbiology, Vol. 7, No. MAR, 262, 07.03.2016.

Research output: Contribution to journalArticle

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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.",
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AU - Zaraket, Hassan

AU - Kondo, Hiroki

AU - Hibino, Akinobu

AU - Yagami, Ren

AU - Odagiri, Takashi

AU - Takemae, Nobuhiro

AU - Tsunekuni, Ryota

AU - Saito, Takehiko

AU - Kimura, Shinji

AU - Kawashima, Takashi

AU - Sato, Isamu

AU - Hibi, Shigeyoshi

AU - Kodo, Naoki

AU - Masaki, Hironori

AU - Shirahige, Yutaka

AU - Asoh, Norichika

AU - Kita, Yoshiko

AU - Kuroki, Reiki

AU - Nawata, Yasuo

AU - Ono, Yasuhiko

AU - Makiya, Tomoko

AU - Takefuta, Kiyotaka

AU - Myint, Yi Yi

AU - Kyaw, Yadanar

AU - Oo, Khin Yi

AU - Tin, Htay Htay

AU - Lin, Nay

AU - Anh, Nguyen Phuong

AU - Hang, Nguyen Le Khanh

AU - Mai, Le Quynh

AU - Hassan, Mohd Rohaizat

AU - Shobugawa, Yugo

AU - Tang, Julian

AU - Dbaibo, Ghassan

AU - Saito, Reiko

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N2 - 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.

AB - 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.

KW - Antiviral

KW - Evolution

KW - Full-genome

KW - Influenza A/H3N2

KW - PB1-F2

KW - Phylogenetic analysis

KW - Reassortment

KW - Vaccine

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