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Article

KAP1 Positively Modulates Influenza A Virus Replication by Interacting with PB2 and NS1 Proteins in Human Lung Epithelial Cells

1
Department of Biopharmacy, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
2
Department of Biology, College of Life Sciences, China Jiliang University, Hangzhou 310018, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Feng Li
Viruses 2022, 14(4), 689; https://doi.org/10.3390/v14040689
Received: 7 March 2022 / Revised: 23 March 2022 / Accepted: 24 March 2022 / Published: 26 March 2022
(This article belongs to the Topic Strategies for Prevention and Control of Influenza)
Influenza virus only encodes a dozen of viral proteins, which need to use host machinery to complete the viral life cycle. Previously, KAP1 was identified as one host protein that potentially interacts with influenza viral proteins in HEK 293 cells. However, the role of KAP1 in influenza virus replication in human lung alveolar epithelial cells and the underlying mechanism remains unclear. In this study, we first generated KAP1 KO A549 cells by CRISPR/Cas9 gene editing. KAP1 deletion had no significant effect on the cell viability and lack of KAP1 expression significantly reduced the influenza A virus replication. Moreover, we demonstrated that KAP1 is involved in the influenza virus entry, transcription/replication of viral genome, and viral protein synthesis in human lung epithelial cells and confirmed that KAP1 interacted with PB2 and NS1 viral proteins during the virus infection. Further study showed that KAP1 inhibited the production of type I IFN and overexpression of KAP1 significantly reduced the IFN-β production. In addition, influenza virus infection induces the deSUMOylation and enhanced phosphorylation of KAP1. Our results suggested that KAP1 is required for the replication of influenza A virus and mediates the replication of influenza A virus by facilitating viral infectivity and synthesis of viral proteins, enhancing viral polymerase activity, and inhibiting the type I IFN production. View Full-Text
Keywords: KAP1; influenza A virus; interacting; PB2 and NS1; replication; human lung epithelial cells KAP1; influenza A virus; interacting; PB2 and NS1; replication; human lung epithelial cells
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MDPI and ACS Style

Feng, H.; Yi, R.; Wu, S.; Wang, G.; Sun, R.; Lin, L.; Zhu, S.; Nie, Z.; He, Y.; Wang, S.; Wang, P.; Shu, J.; Wu, L. KAP1 Positively Modulates Influenza A Virus Replication by Interacting with PB2 and NS1 Proteins in Human Lung Epithelial Cells. Viruses 2022, 14, 689. https://doi.org/10.3390/v14040689

AMA Style

Feng H, Yi R, Wu S, Wang G, Sun R, Lin L, Zhu S, Nie Z, He Y, Wang S, Wang P, Shu J, Wu L. KAP1 Positively Modulates Influenza A Virus Replication by Interacting with PB2 and NS1 Proteins in Human Lung Epithelial Cells. Viruses. 2022; 14(4):689. https://doi.org/10.3390/v14040689

Chicago/Turabian Style

Feng, Huapeng, Ruonan Yi, Shixiang Wu, Genzhu Wang, Ruolin Sun, Liming Lin, Shunfan Zhu, Zhenyu Nie, Yulong He, Siquan Wang, Pei Wang, Jianhong Shu, and Li Wu. 2022. "KAP1 Positively Modulates Influenza A Virus Replication by Interacting with PB2 and NS1 Proteins in Human Lung Epithelial Cells" Viruses 14, no. 4: 689. https://doi.org/10.3390/v14040689

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