Analysis of the Neuraminidase Amino Acid Sequences of Influenza A/H1N1pdm09, A/H3N2, and B Viruses Isolated from Influenza Patients in the 2013/14 Japanese Influenza Season

Hideyuki Ikematsu, Yong Jeong, Kenjiro Shirane, Hidehiro Toh, Hiroyuki Sasaki, Yui Koga, Shinya Matsumoto, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang

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Abstract

BACKGROUND: Neuraminidase (NA) is an essential surface protein for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50% inhibitory concentration (IC50) of four NA inhibitors.

MATERIALS AND METHODS: A total of 20 viruses that showed high or low IC50 of NA inhibitors were selected from A/H1N1pdm09, A/H3N2, and B isolates from the viruses isolated from patients in the 2013-14 influenza season. Viral RNA was extracted and RT-PCR was done. The amplified genome was sequenced using a next generation sequencer", and the deduced amino acid sequences were analyzed.

RESULTS: Two A/H1N1pdm09 viruses that showed very high IC50 for oseltamivir (150 nM and 130 nM) contained the H275Y mutation. Otherwise, no significant relation was found between the NA amino acids and the IC50 of the four NA inhibitors. There was no significant relation between the NA amino acids and the IC50 of the four NA inhibitors for A/H3N2 viruses. The B viruses that showed a high IC50 for oseltamivir and laninamivir shared some amino acids. The B viruses that showed a high IC50 of zanamivir and peramivir also shared some amino acids. They were different from the shared amino acids found for oseltamivir and laninamivir.

CONCLUSION: The previously reported H275Y mutation that causes oseltamivir resistance was found in the two A/H1N1pdm09 viruses that showed a very high IC50 for oseltamivir. No additional NA amino acid sequences related to the IC50 of the four NA inhibitors was found. The meaning of the shared amino acids among B viruses that showed a high IC50 would be an interesting target for further investigation.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
JournalFukuoka igaku zasshi = Hukuoka acta medica
Volume106
Issue number8
Publication statusPublished - Aug 1 2015

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H3N2 Subtype Influenza A Virus
Cercopithecine Herpesvirus 1
Protein Sequence Analysis
Neuraminidase
Human Influenza
Inhibitory Concentration 50
Oseltamivir
R 125489
Amino Acids
Amino Acid Sequence
Viruses
Orthomyxoviridae
Mutation
Zanamivir
Viral RNA
Virus Replication

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Analysis of the Neuraminidase Amino Acid Sequences of Influenza A/H1N1pdm09, A/H3N2, and B Viruses Isolated from Influenza Patients in the 2013/14 Japanese Influenza Season. / Ikematsu, Hideyuki; Jeong, Yong; Shirane, Kenjiro; Toh, Hidehiro; Sasaki, Hiroyuki; Koga, Yui; Matsumoto, Shinya; Hotta, Taeko; Uchiumi, Takeshi; Kang, Dongchon.

In: Fukuoka igaku zasshi = Hukuoka acta medica, Vol. 106, No. 8, 01.08.2015, p. 231-239.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Neuraminidase (NA) is an essential surface protein for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50{\%} inhibitory concentration (IC50) of four NA inhibitors.MATERIALS AND METHODS: A total of 20 viruses that showed high or low IC50 of NA inhibitors were selected from A/H1N1pdm09, A/H3N2, and B isolates from the viruses isolated from patients in the 2013-14 influenza season. Viral RNA was extracted and RT-PCR was done. The amplified genome was sequenced using a next generation sequencer{"}, and the deduced amino acid sequences were analyzed.RESULTS: Two A/H1N1pdm09 viruses that showed very high IC50 for oseltamivir (150 nM and 130 nM) contained the H275Y mutation. Otherwise, no significant relation was found between the NA amino acids and the IC50 of the four NA inhibitors. There was no significant relation between the NA amino acids and the IC50 of the four NA inhibitors for A/H3N2 viruses. The B viruses that showed a high IC50 for oseltamivir and laninamivir shared some amino acids. The B viruses that showed a high IC50 of zanamivir and peramivir also shared some amino acids. They were different from the shared amino acids found for oseltamivir and laninamivir.CONCLUSION: The previously reported H275Y mutation that causes oseltamivir resistance was found in the two A/H1N1pdm09 viruses that showed a very high IC50 for oseltamivir. No additional NA amino acid sequences related to the IC50 of the four NA inhibitors was found. The meaning of the shared amino acids among B viruses that showed a high IC50 would be an interesting target for further investigation.",
author = "Hideyuki Ikematsu and Yong Jeong and Kenjiro Shirane and Hidehiro Toh and Hiroyuki Sasaki and Yui Koga and Shinya Matsumoto and Taeko Hotta and Takeshi Uchiumi and Dongchon Kang",
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T1 - Analysis of the Neuraminidase Amino Acid Sequences of Influenza A/H1N1pdm09, A/H3N2, and B Viruses Isolated from Influenza Patients in the 2013/14 Japanese Influenza Season

AU - Ikematsu, Hideyuki

AU - Jeong, Yong

AU - Shirane, Kenjiro

AU - Toh, Hidehiro

AU - Sasaki, Hiroyuki

AU - Koga, Yui

AU - Matsumoto, Shinya

AU - Hotta, Taeko

AU - Uchiumi, Takeshi

AU - Kang, Dongchon

PY - 2015/8/1

Y1 - 2015/8/1

N2 - BACKGROUND: Neuraminidase (NA) is an essential surface protein for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50% inhibitory concentration (IC50) of four NA inhibitors.MATERIALS AND METHODS: A total of 20 viruses that showed high or low IC50 of NA inhibitors were selected from A/H1N1pdm09, A/H3N2, and B isolates from the viruses isolated from patients in the 2013-14 influenza season. Viral RNA was extracted and RT-PCR was done. The amplified genome was sequenced using a next generation sequencer", and the deduced amino acid sequences were analyzed.RESULTS: Two A/H1N1pdm09 viruses that showed very high IC50 for oseltamivir (150 nM and 130 nM) contained the H275Y mutation. Otherwise, no significant relation was found between the NA amino acids and the IC50 of the four NA inhibitors. There was no significant relation between the NA amino acids and the IC50 of the four NA inhibitors for A/H3N2 viruses. The B viruses that showed a high IC50 for oseltamivir and laninamivir shared some amino acids. The B viruses that showed a high IC50 of zanamivir and peramivir also shared some amino acids. They were different from the shared amino acids found for oseltamivir and laninamivir.CONCLUSION: The previously reported H275Y mutation that causes oseltamivir resistance was found in the two A/H1N1pdm09 viruses that showed a very high IC50 for oseltamivir. No additional NA amino acid sequences related to the IC50 of the four NA inhibitors was found. The meaning of the shared amino acids among B viruses that showed a high IC50 would be an interesting target for further investigation.

AB - BACKGROUND: Neuraminidase (NA) is an essential surface protein for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50% inhibitory concentration (IC50) of four NA inhibitors.MATERIALS AND METHODS: A total of 20 viruses that showed high or low IC50 of NA inhibitors were selected from A/H1N1pdm09, A/H3N2, and B isolates from the viruses isolated from patients in the 2013-14 influenza season. Viral RNA was extracted and RT-PCR was done. The amplified genome was sequenced using a next generation sequencer", and the deduced amino acid sequences were analyzed.RESULTS: Two A/H1N1pdm09 viruses that showed very high IC50 for oseltamivir (150 nM and 130 nM) contained the H275Y mutation. Otherwise, no significant relation was found between the NA amino acids and the IC50 of the four NA inhibitors. There was no significant relation between the NA amino acids and the IC50 of the four NA inhibitors for A/H3N2 viruses. The B viruses that showed a high IC50 for oseltamivir and laninamivir shared some amino acids. The B viruses that showed a high IC50 of zanamivir and peramivir also shared some amino acids. They were different from the shared amino acids found for oseltamivir and laninamivir.CONCLUSION: The previously reported H275Y mutation that causes oseltamivir resistance was found in the two A/H1N1pdm09 viruses that showed a very high IC50 for oseltamivir. No additional NA amino acid sequences related to the IC50 of the four NA inhibitors was found. The meaning of the shared amino acids among B viruses that showed a high IC50 would be an interesting target for further investigation.

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