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

Abstract

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.

Harnessing the Noncanonical Keap1-Nrf2 Pathway for Human Cytomegalovirus Control

“…Lee et al also observed that Nrf2 played a role in cell viability during infection under oxidative stress but not under normal culture conditions ( 46 ). Nrf2 activation has also been associated with an antiviral program and repression of herpes simplex virus 1 replication ( 52 , 53 ). In our findings, total Nrf2 levels were decreased during the late stage of infection (72 hpi) but stabilized with ARP101 ( Fig.…”

Honokiol Inhibits SARS-CoV-2 Replication in Cell Culture at a Post-Entry Step

“…Other targets of HK include Sirt3 ( 19 ), Nrf2 ( 26 ), MAPK ( 27 ), and SMAD ( 28 ) signaling pathways. Some of these factors, such as Nrf2, Sirt3, and mTOR ( 29 – 31 ), have been linked to pathways involved in antiviral responses. HK has also been shown to possess antiviral effects against a broad range of different viruses, such as hepatitis C virus ( 16 ), dengue virus ( 15 ), herpes simplex virus 1 ( 17 ), Usutu virus ( 32 ), and Mayaro virus ( 33 ).…”

Therapeutic Potential of Biochanin A in Herpes Simplex Keratitis

“…The treatment mechanisms of BCA on HSK are still in their infancy and can be progressed in multiple aspects. Firstly, prior studies have reported that the upregulation of Nrf2 activity restricted HSV-1 viral infection [ 49 , 50 ], and isoflavones have the ability to activate Nrf2 [ 51 ]. Several studies have confirmed that BCA has the ability to activate Nrf2 [ 52 , 53 ], and our study determined it too.…”