Histone acetyl transferase TIP60 inhibits the replication of influenza a virus by activation the TBK1-IRF3 pathway

Jiajun Ma,Yungfu Chang,Hongxuan He,Meng Li,Jing Luo,Bo Wang,Juan Du,Guoyao Ma,Lin Chen,Chengmin Wang,Chengmei Huang

doi:10.1186/s12985-018-1079-3

Abstract

Influenza A virus (IAV) is an important pathogen that poses a severe threat to the health of humans. Nucleoprotein (NP) of IAV plays crucial roles in the viral life cycle by interacting with various cellular factors. Histone Acetyl Transferase TIP60 is a key target of several viral proteins during infection, including HIV-1 Tat, HPV E6, HTLV-1 p30II and HCMV UL27 proteins. However, Whether the interaction between the IAV NP and TIP60, and the role of TIP60 in IAV life cycle are largely unknown. Here, we showed that IAV infection up-regulated TIP60 protein and RNA expression. Overexpression of TIP60 inhibited viral protein and RNA expression and reduced the progeny viral titer. Further study revealed that TIP60 inhibited viral replication through activation of TBK1-IRF3 signaling pathway. Furthermore, we demonstrated that the NP protein of IAV interacted with TIP60. Together, these results indicate that TIP60 play a repressor in IAV infection, and it may be a possible target for antiviral drugs.

Highlights

Influenza A virus (IAV) is a critical respiratory pathogen that belongs to the Orthomyxoviridae family, which causes severe morbidity and mortality rates every year [1]
IAVs have negative-stranded RNA genomes consisting of eight RNA segments, and encode up to 17 proteins: hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), polymerase basic protein 1(PB1), polymerase basic protein 2 (PB2), Polymerase basic protein 1 (PB1)-F2, PB1-N40, polymerase acidic protein (PA), Polymerase acidic protein (PA)-X, PA-N155, PA-N182, matrix protein 1 (M1), M2 and M42, nonstructural protein1 (NS1), NS2, NS3 [2,3,4,5,6,7,8]
TIP60 is a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) family of histone acetyltransferase that was found by interaction with the HIV type 1 (HIV-1) Tat protein [12, 13]

Summary

Introduction

Influenza A virus (IAV) is a critical respiratory pathogen that belongs to the Orthomyxoviridae family, which causes severe morbidity and mortality rates every year [1]. IAVs have negative-stranded RNA genomes consisting of eight RNA segments, and encode up to 17 proteins: hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), polymerase basic protein 1(PB1), polymerase basic protein 2 (PB2), PB1-F2, PB1-N40, polymerase acidic protein (PA), PA-X, PA-N155, PA-N182, matrix protein 1 (M1), M2 and M42, nonstructural protein (NS1), NS2, NS3 [2,3,4,5,6,7,8]. TIP60 is a member of the MYST (MOZ, Ybf2/Sas, Sas, and TIP60) family of histone acetyltransferase that was found by interaction with the HIV-1 Tat protein [12, 13]. It contains an N-terminal chromodomain and a C-terminal conserved MYST domain (HAT domain and Cys-Cys-His-Cys zinc finger). Expression of TIP60 is observed in multiple cell lines and tissues, and its homologues have been identified in chicken, mouse, and human [15]

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Conclusion