Table 1.

Viruses and NRF2 among publications.

Virus	Model	Effect on NRF2	Viral Replication	Patho/Cytoprotective effect	Mechanism	Ref
HIV	In vitro expression of HIV protein tat in neuroblastoma cell line	↑	ND		Induction of ROS	[20]
	In vitro infection of primary human monocytes and in vivo rat	↓	ND		ND	[41]
RSV	In vitro with human alveolar basal epithelial cell line	↑	↓		ND	[21]
	In vivo with Nrf2+/+ and Nrf2−/− mice	↑	↓		ND	[45]
	In vivo with mice and in vitro with human alveolar basal epithelial cell line	↓	ND		Proteasomal degradation of Nrf2	[22]
	In vitro with human alveolar epithelial cell line	↓	ND		SUMOylation and ubiquitination of Nrf2 induce its degradation	[42]
SFTSV	In vivo with mice	↑	ND	Pathogenic: mice infected with SFTSV mutated for this nonstructural protein showed a higher survival rate and less weight loss.	SFTSV viral protein interact with TRIM21 that normally mediated p62 ubiquitination. Hence p62 is stabilized and interact with KEAP1 leading to set free Nrf2	[23]
HCV	In vitro with hepatocyte cell line	↑	ND		HCV core proteins activate Nrf2/ARE pathway via several independent mechanisms. 1. Nrf2 activation was triggered by protein kinase C in response to accumulation of ROS. 2. Nrf2 was also activated in ROS independent manner 3. The effect of some viral proteins was mediated through casein kinase 2 and phosphoinositide 3 kinase.	[24]
	In vitro with hepatocyte cell line	↓	ND		HCV Core and nonstructural proteins induce nuclear export of sMaf a Nrf2 partner	[40]
	In vitro with hepatocellular carcinoma cell line	ND	ND	Pathogenic: Persistent activation of NRF2 makes HCV positive tumor cells resistant to oxidative damage and anticancer agent		[55]
HCMV	In vitro with primary human foreskin fibroblasts	↑	↓		Casein Kinase 2 mediated	[27]
HBV	In vitro with human hepatoma derived cell lines	↑	ND		Triggered by HBV proteins (HBx and LHBs)	[25]
	In vitro with human hepatocyte cell lines	↑	ND		HBV protein HBx stimulate p62-Keap1 interaction leading to Nrf2 activation	[26]
MARV	In vitro with human kidney cell line	↑	ND	Pathogenic: Infected mice deficient for Nrf2 have a higher survival rate than infected control mice	VP24 viral protein bind to KEAP1 setting free Nrf2	[18]
	In vitro with lymphocyte cell line	↑	↓	Cytoprotective: Activation of antioxidant mechanisms	MARV protein Mvp24 interact directly with KEAP1	[19]
KSHV	In vitro with Human dermal microvascular endothelial cell line	↑	ND	Pathogenic: Nrf2 contribute to the expression of host factor VEGF-A, VEGF-D and COX-2 important for KSHV pathogenesis	Induction of ROS	[30]
	In vitro with primary effusion lymphoma cell line and tissue	↑	↑		COX-2/PGE2 axis induces Nrf2 through prostaglandin E receptor 4 (EP4)	[32]
	In vitro with TIVE and LTC cells	↑	↑		Two distinct mechanisms: (1) Ros induction. (2) ROS-independent and through P62–Keap1 interaction	[31]
IAV	In vitro with alveolar type II cells and alveolar macrophages isolated from human lungs infected	↑	↓		ND	[34]
	Primary human nasal epithelial cell	ND	↓		ND	[46]
	In vitro Madin darby canine kidney cell line	ND	↓		ND	[47]
HSV1	In vitro with primary normal human dermal fibroblast cell line	↑	↓		ND	[33]
TBEV	In vitro with human embryonic kidney cell line	↑	ND		TBEV nonstructural protein induces ROS production	[35]
Broad	In vitro chemical activation of NRF2 before infection inhibited replication of HSV-1/2,VACV, ZKV, SARS-CoV2	↑	↓		ND	[16]
DENV	In vitro with murine monocytic cell line	↑	ND		DENV infection induces ER stress that phosphorylate PERK that activate Nrf2	[37]
	In vitro with monocyte isolated from human peripheral blood mononuclear cell from healthy donors	↑	ND		ND	[36]
RHDV	In vivo with rabbits	↓	ND	Cytoprotective: Upregulation of NRF2 reduce infected rabbit’s death rate	Nuclear export of Nrf2 by KEAP1-NFκB complex	[44]
EV71	In vitro with human rhabdomyosarcoma cell line	↓	↓		Up regulation of Keap1	[38]
CMV	In vivo with mice Nrf2−/− and Nrf2+/+	ND	↓		ND	[51]
ZIKV	In vitro with primary human macrophages	ND	↓		ND	[49]
EBOV	In vitro with human cell lines	ND	↓		ND	[48]
RV	In vitro with human cell lines	ND	↓		ND	[50]
	In vitro with green monkey fetal kidney cell line	↓	ND		Proteasomal degradation dependency	[39]
CVB3	In vitro with mice cardiomyocytes and in vivo with mice	↓	ND	Contribute to oxidative stress		[43]

ND: not determined.