Details:

Alternative Title:
PLoS One
Personal Author:
Yang, Ji-Rong ; Lin, Yu-Cheng ; Huang, Yuan-Pin ; Su, Chun-Hui ; Lo, Je ; ... More +
Yang, Ji-Rong ; Lin, Yu-Cheng ; Huang, Yuan-Pin ; Su, Chun-Hui ; Lo, Je ; Ho, Yu-Lin ; Yao, Ching-Yuan ; Hsu, Li-Ching ; Wu, Ho-Sheng ; Liu, Ming-Tsan Less -
Description:
A dramatic increase in the frequency of the H275Y mutation in the neuraminidase (NA), conferring resistance to oseltamivir, has been detected in human seasonal influenza A/H1N1 viruses since the influenza season of 2007-2008. The resistant viruses emerged in the ratio of 14.3% and quickly reached 100% in Taiwan from September to December 2008. To explore the mechanisms responsible for emergence and spread of the resistant viruses, we analyzed the complete genome sequences of 25 viruses collected during 2005-2009 in Taiwan, which were chosen from various clade viruses, 1, 2A, 2B-1, 2B-2, 2C-1 and 2C-2 by the classification of hemagglutinin (HA) sequences. Our data revealed that the dominant variant, clade 2B-1, in the 2007-2008 influenza emerged through an intra-subtype 4+4 reassortment between clade 1 and 2 viruses. The dominant variant acquired additional substitutions, including A206T in HA, H275Y and D354G in NA, L30R and H41P in PB1-F2, and V411I and P453S in basic polymerase 2 (PB2) proteins and subsequently caused the 2008-2009 influenza epidemic in Taiwan, accompanying the widespread oseltamivir-resistant viruses. We also characterized another 3+5 reassortant virus which became double resistant to oseltamivir and amantadine. Comparison of oseltamivir-resistant influenza A/H1N1 viruses belonging to various clades in our study highlighted that both reassortment and mutations were associated with emergence and spread of these viruses and the specific mutation, H275Y, conferring to antiviral resistance, was acquired in a hitch-hiking mechanism during the viral evolutionary processes.
Subjects:
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Animals Antiviral Agents Cell Line Dogs Drug Resistance, Viral Epidemics Humans Influenza, Human Influenza A Virus, H1N1 Subtype Molecular Sequence Data Mutation Neuraminidase Oseltamivir Reassortant Viruses
Source:
PLoS One. 6(3).
Document Type:
Journal Article
Place as Subject:
Taiwan
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:e3674e1eb18aee0170473a4b319cdf475d84e1ce68ef2b58c477f9e329802e50
Download URL:
https://stacks.cdc.gov/view/cdc/4315/cdc_4315_DS1.pdf
File Type:

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