The effect of mutations derived from mouse-adapted H3N2 seasonal influenza A virus to pathogenicity and host adaptation


Autoři: Eun-Ji Choi aff001;  Young Jae Lee aff001;  Jin-Moo Lee aff001;  Yeon-Jung Kim aff001;  Jang-Hoon Choi aff001;  Byeongwoo Ahn aff002;  Kisoon Kim aff001;  Myung Guk Han aff001
Působiště autorů: Division of Viral Disease Research, Center for Infectious Diseases Research, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong, Republic of Korea aff001;  College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227516

Souhrn

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.

Klíčová slova:

Death rates – Influenza A virus – Microbial mutation – Mouse models – Pathogenesis – Substitution mutation – Viral pathogens – Viral replication


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