Inter-Fighting between Influenza A Virus NS1 and β-TrCP: A Novel Mechanism of Anti-Influenza Virus

Abstract

Influenza A virus (IAV) prevents innate immune signaling during infection. In our previous study, the production of pro-inflammatory cytokines was associated with Cullin-1 RING ligase (CRL1), which was related to NF-κB activation. However, the underlying mechanism is unclear. Here, an E3 ligase, β-transducin repeat-containing protein (β-TrCP), was significantly downregulated during IAV infection. Co-IP analysis revealed that non-structural 1 protein (NS1) interacts with β-TrCP. With co-transfection, an increase in NS1 expression led to a reduction in β-TrCP expression, affecting the level of IκBα and then resulting in repression of the activation of the NF-κB pathway during IAV infection. In addition, β-TrCP targets the viral NS1 protein and significantly reduces the replication level of influenza virus. Our results provide a novel mechanism for influenza to modulate its immune response during infection, and β-TrCP may be a novel target for influenza virus antagonism.

Influenza Virus Host Restriction Factors: The ISGs and Non-ISGs

“…β-TrCP (β-transducin repeat-containing protein), an E3 ligase, inhibits influenza virus infection, but viral NS1 overcomes the β-TrCP restriction by inducing its degradation in infected cells [ 280 ].…”

Research progress on the nonstructural protein 1 (NS1) of influenza a virus

“… A/PR/8/34 (H1N1), A/H1N1pdm09, A/Oklahoma/309/06 (H3N2) [ 45 ] 2022 NS1 inhibits innate immunity by acting on β-transducin repeat-containing protein (β-TrCP) A549, MDCK, and 293T cells. A/California/04/09 (H1N1), A/PR/8/34 (H1N1) [ 46 ] 2022 The interaction between the RBD domain of NS1 and TRBP affects the RNAi mechanism of the host. 293T cells.…”