The Influenza Virus Protein PB1-F2 Increases Viral Pathogenesis through Neutrophil Recruitment and NK Cells Inhibition

被引:35
作者
Vidy, Aurore [1 ]
Maisonnasse, Pauline [1 ]
Da Costa, Bruno [1 ]
Delmas, Bernard [1 ]
Chevalier, Christophe [1 ]
Le Goffic, Ronan [1 ]
机构
[1] Univ Paris Saclay, INRA, VIM, F-78350 Jouy En Josas, France
关键词
LUNG INJURY; HEMAGGLUTININS; RECOGNITION; ACTIVATION; EXPRESSION; BACTERIAL; MEMBRANE; INNATE;
D O I
10.1371/journal.pone.0165361
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The influenza A virus (IAV) PB1-F2 protein is a virulence factor contributing to the pathogenesis observed during IAV infections in mammals. In this study, using a mouse model, we compared the host response associated with PB1-F2 with an early transcriptomic signature that was previously associated with neutrophils and consecutively fatal IAV infections. This allowed us to show that PB1-F2 is partly involved in neutrophil-related mechanisms leading to death. Using neutropenic mice, we confirmed that the harmful effect of PB1-F2 is due to an excessive inflammation mediated by an increased neutrophil mobilization. We identified the downstream effects of this PB1-F2-exacerbated neutrophil recruitment. PB1-F2 had no impact on the lymphocyte recruitment in the airways at day 8 pi. However, functional genomics analysis and flow cytometry in broncho-alveolar lavages at 4 days pi revealed that PB1-F2 induced a NK cells deficiency. Thus, our results identify PB1-F2 as an important immune disruptive factor during the IAV infection.
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页数:19
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