Upregulation of nuclear factor E2-related factor 2 (Nrf2) represses the replication of herpes simplex virus type 1

Background: Nuclear factor E2-related factor 2 (Nrf2) is an important transcription factor which plays a pivotal role in detoxifying Reactive Oxygen Species (ROS) and has been more recently shown to regulate inflammatory and Antiviral responses. However, the role of Nrf2 in Herpes Simplex Virus type 1 (HSV-1) Infection is still unclear. In this study, the interaction between the Nrf2 and HSV-1 replication was investigated.

Methods: The levels of oxidative stress was monitored by using 8-hydroxy-2'-deoxyguanosine (8-OHdG) ELISA kits, and the dynamic changes of Nrf2-antioxidant response element (Nrf2-ARE) pathway were detected by Western Blot. The effect of Nrf2-ARE pathway on the regulation of HSV-1 proliferation was analyzed by Western Blot, Real-Time PCR and TCID₅₀ assay.

Results: HSV-1 Infection induced oxidative stress. Nrf2 was activated, accompanied by the increase of its down-stream antioxidant Enzyme heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) in the early stage of HSV-1 Infection. The proliferation of HSV-1 was inhibited by overexpression of Nrf2 or treatment with its activator tert-Butylhydroquinone (tBHQ). On the contrary, silencing of Nrf2 promotes virus replication. HO-1 is involved in the regulation of IFN response, leading to efficient anti-HSV-1 effects.

Conclusion: Our observations indicate that the Nrf2-ARE pathway activates a passive defensive response in the early stage of HSV-1 Infection. Targeting the Nrf2 pathway demonstrates the potential for combating HSV-1 Infection.