[Source: PLOS One, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
The effect of mutations derived from mouse-adapted H3N2 seasonal influenza A virus to pathogenicity and host adaptation
Eun-Ji Choi , Young Jae Lee , Jin-Moo Lee, Yeon-Jung Kim, Jang-Hoon Choi, Byeongwoo Ahn, Kisoon Kim, Myung Guk Han
Published: January 9, 2020 / DOI: https://doi.org/10.1371/journal.pone.0227516
Elucidating the genetic basis of influenza A viruses (IAVs) is important to understand which mutations will determine the virulence and the host range of mammals. Here, seasonal H3N2 influenza was adapted in mice by serial passage and four mutants, each carrying amino acid substitutions related to mouse adaptation in either the PB2, HA, NP, or NA protein, were generated. To confirm the contribution of each gene to enhanced pathogenicity and mouse adaptation, mice were inoculated with the respective variants, and virulence, replication, histopathology, and infectivity were examined. The virus harboring HA mutations displayed increased infection efficiency and replication competence, resulting in higher mortality in mice relative to those infected with wild-type virus. By contrast, the NP D34N mutation caused rapid and widespread infection in multiple organs without presenting virulent symptoms. Additionally, the PB2 F323L mutation presented delayed but elevated replication competence in the respiratory tract, whereas the S331R mutation in NA showed no considerable effects on mouse adaptation. These results suggested that mouse-adapted changes in HA are major factors in increased pathogenicity and that mutations in NP and PB2 also contribute to cross-species adaptability. Our findings offer a better understanding of the molecular basis for IAV pathogenicity and adaptation in a new host.
Citation: Choi E-J, Lee YJ, Lee J-M, Kim Y-J, Choi J-H, Ahn B, et al. (2020) The effect of mutations derived from mouse-adapted H3N2 seasonal influenza A virus to pathogenicity and host adaptation. PLoS ONE 15(1): e0227516. https://doi.org/10.1371/journal.pone.0227516
Editor: Man-Seong Park, Korea University College of Medicine and School of Medicine, REPUBLIC OF KOREA
Received: August 7, 2019; Accepted: December 19, 2019; Published: January 9, 2020
Copyright: © 2020 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: This work was supported by grants of the National Institute of Health, Korea (2017-NI43001 and 2014-ER4301-02). The funder provided experiment resources, equipment, reagents and space, and helped to complete manuscript by pay the cost for English proofreading service, http://www.cdc.go.kr/index.es?sid=a5. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Keywords: Influenza A; H3N2; Viral pathogenesis; Animal models.