期刊
VIROLOGY
卷 516, 期 -, 页码 71-75出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2018.01.004
关键词
Influenza; PA-X; Shutoff; Yeasts
类别
资金
- Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) from Japan Agency for Medical Research and Development (AMED)
- Leading Advanced Projects for medical innovation (LEAP) from AMED
- e-ASIA Joint Research Program from AMED
- Ministry of Education, Culture, Science, Sports, and Technology (MEXT) of Japan [16H06429, 16K21723, 16H06434]
- Center for Research on Influenza Pathogenesis (CRIP) - NIAID [HHSN272201400008C]
- NIH [U19 AI 107810]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI107810] Funding Source: NIH RePORTER
The influenza A virus protein PA-X comprises an N-terminal PA region and a C-terminal PA-X-specific region. PA-X suppresses host gene expression, termed shutoff, via mRNA cleavage. Although the endonuclease active site in the N-terminal PA region of PA-X and basic amino acids in the C-terminal PA-X-specific region are known to be important for PA-X shutoff activity, other amino acids may also play a role. Here, we used yeast to identify novel amino acids of PA-X that are important for PA-X shutoff activity. Unlike wild-type PA-X, most PA-X mutants predominantly localized in the cytoplasm, indicating that these mutations decreased the shutoff activity of PA-X by affecting PA-X translocation to the nucleus. Mapping of the identified amino acids onto the N-terminal structure of PA revealed that some of them likely contribute to the formation of the endonuclease active site of PA.
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