Mutations in NA that induced low pH-stability and enhanced the replication of pandemic (H1N1) 2009 influenza A virus at an early stage of the pandemic

Tadanobu Takahashi; Jiasheng Song; Takashi Suzuki; Yoshihiro Kawaoka

doi:10.1371/journal.pone.0064439

Mutations in NA that induced low pH-stability and enhanced the replication of pandemic (H1N1) 2009 influenza A virus at an early stage of the pandemic

PLoS One. 2013 May 16;8(5):e64439. doi: 10.1371/journal.pone.0064439. Print 2013.

Authors

Tadanobu Takahashi¹, Jiasheng Song, Takashi Suzuki, Yoshihiro Kawaoka

Affiliation

¹ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.

Abstract

An influenza A virus that originated in pigs caused a pandemic in 2009. The sialidase activity of the neuraminidase (NA) of previous pandemic influenza A viruses are stable at low pH (≤5). Here, we identified the amino acids responsible for this property. We found differences in low-pH stability at pH 5.0 among pandemic (H1N1) 2009 viruses, which enhanced the replication of these viruses. Low-pH-stable NA enhancement of virus replication may have contributed to the rapid worldwide spread and adaptation to humans of pandemic (H1N1) 2009 viruses during the early stages of the 2009 pandemic.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Humans
Hydrogen-Ion Concentration
Influenza A virus / enzymology*
Influenza A virus / genetics
Influenza A virus / pathogenicity
Influenza, Human / virology*
Mutation
Neuraminidase / genetics*
Pandemics
Phylogeny
Virus Replication / genetics
Virus Replication / physiology

Substances

Neuraminidase

Grants and funding

This work was supported, in part, by a MEXT/JSPS KAKENHI Grant (Number C; 23590549), by a Sasakawa Scientific Research Grant from The Japan Science Society, by a SRI (Shizuoka Research Institute) academic research grant, by the Global COE Program from the Japan Society for the Promotion of Science, by ERATO (Japan Science and Technology Agency), by a grant-in-aid for Specially Promoted Research from the Ministries of Education, Culture, Sports, Science, and Technology, by grants-in-aid from Health, Labor, and Welfare of Japan, by the Japan Initiative for Global Research Network on Infectious Diseases from the Ministries of Education, Culture, Sports, Science, and Technology, and by National Institute of Allergy and Infectious Disease Public Health Service research grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.