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Evidence for a novel mechanism of influenza A virus host adaptation modulated by PB 2‐627
Author(s) -
Liu Xiaokun,
Yang Cha,
Sun Xiaomei,
Lin Xian,
Zhao Lianzhong,
Chen Huanchun,
Jin Meilin
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14867
Subject(s) - biology , virus , influenza a virus , virology , influenza a virus subtype h5n1 , histone , viral replication , mutant , gene , genetics
Influenza virus cross‐species transmission is restricted by the host, but viruses overcome this restriction by accumulating mutations which allow them to adapt to a new host. Among the many factors which facilitate virus host adaptation, polymerase basic protein 2 ( PB 2 ) 627 plays an important role, although the underlying molecular mechanism has not been fully understood. In a previous study, we found that histone H1.2 (encoded by HIST 1H1C ) regulates human or avian influenza virus replication in different ways, indicating that it might be involved in virus host adaptation. Herein, we found that HIST 1H1C expression, phosphorylation and methylation levels are decreased when infected with H1N1 influenza virus and increased when infected with H5N1 influenza virus. Overexpressing the eight gene segments of the influenza virus, we found that only PB 2 significantly affects HIST 1H1C expression and modifications. Since the 627 site is different between the H5N1 and H1N1 influenza viruses we constructed PB 2‐627E (avian variant) and PB 2‐627K (human variant) mutant viruses, and observed that the effects of the wild‐type and the mutant viruses on HIST 1H1C expression and modifications are the opposite of one another. Further analysis showed that influenza virus PB 2‐627 regulates HIST 1H1C expression via Sp1 , and specifically that PB 2‐627K down‐regulates Sp1 and HIST 1H1C while PB 2‐627E up‐regulates Sp1 and HIST 1H1C . In addition, HIST 1H1C can feedback regulate DNA‐dependent protein kinase and euchromatic histone‐lysine N ‐methyltransferase 1/2, leading to altered HIST 1H1C phosphorylation and methylation levels, and affecting influenza virus replication accordingly. In summary, this study illustrates the mechanism of PB 2‐627E/K ‐mediated regulation of influenza virus host adaptation.