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Basic Characteristics of Mutations
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Mutation Site
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K249E |
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Mutation Site Sentence
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D199N in A/H1N1pdm09, D151E, K249E, G320E, and S331R in A/H3N2, and I262T in B were extracted as RI/HRI-related AA mutations, based on their related references6, 24, 25, 26; however, no virus harboring these AA mutations showed substantial RI/HRI based on their IC50 values. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NA |
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Standardized Encoding Gene
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NA
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Genotype/Subtype
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H3N2 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Influenza A
Influenza B
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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NAI |
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Location
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Japan |
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Literature Information
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PMID
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30548432
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Title
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Consecutive influenza surveillance of neuraminidase mutations and neuraminidase inhibitor resistance in Japan
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Author
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Chong Y,Matsumoto S,Kang D,Ikematsu H
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Journal
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Influenza and other respiratory viruses
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Journal Info
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2019 Mar;13(2):115-122
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Abstract
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BACKGROUND: The large consumption of neuraminidase inhibitors (NAIs) for the treatment of influenza virus infections places Japan at risk of becoming the epicenter of the global spread of NAI-resistant viruses. OBJECTIVE: To clarify NA amino acid mutations of epidemic influenza viruses in Japan and their related NAI resistance. METHODS: A total of 1791 samples, including 396 A/H1N1pdm09, 1117 A/H3N2, and 278 B isolates, were collected to determine of their 50% inhibitory concentration (IC(50) ) values by NAIs (oseltamivir, zanamivir, peramivir, and laninamivir) during the Japanese seasons from 2011-2012 to 2016-2017. Then, 380 samples including 49 A/H1N1pdm09, 251 A/H3N2, and 80 B isolates were sequenced for the entire NA genes. RESULTS: Neuraminidase inhibitor-resistant A/H1N1pdm09 viruses were detected at a frequency of 1.3% (5/396 isolates) in the epidemic seasons. None of the A/H3N2 and B viruses developed resistance to any of the four NAIs during the six seasons. Only five and 13 AA mutations were detected in the NA catalytic sites of A/H1N1pdm09 and A/H3N2 viruses, respectively. No mutations were observed in the catalytic sites of B viruses. Four of the five mutations in the catalytic sites of A/H1N1pdm09 consisted of H275Y, which was related to high resistance to oseltamivir and peramivir. Most (10/13) of the catalytic site mutations in A/H3N2 were associated with MDCK-passaged induction (D151G/N). Finally, no mutations related to substantial NAI resistance were detected in the A/H3N2 and B viruses examined. CONCLUSION: These findings suggest that the NA catalytic sites of influenza viruses are well preserved. Even in Japan, no spread of NAI-resistant viruses has been observed, and A/H1N1pdm09 viruses carrying H275Y remain limited.
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Sequence Data
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LC406948-LC407103;LC408965-LC409058;LC409129-LC409257
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