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• A long list of IFN-I regulation genes screened in PBMCs of HIV-1 infected patients. • For the first time, we found USP18 upregulated in HIV-1 infected individuals. • Ubiquitin associated processes are vital in regulation of IFN-I signaling. Chronic activation of the innate immune system plays a central role in HIV-1 disease progression. Negative regulation of innate immunity is critical in preventing the effects of this excessive activation; however, the molecules involved in this process remain to be identified. In this study, we compared the expression of immune regulation genes between HIV-1 infected individuals and healthy control participants to identify genes involved in the regulation of innate immunity in HIV-1 infection. We conducted gene expression analysis of a series of immune regulatory genes in viremic treatment-naïve HIV-positive donors, patients receiving highly active antiretroviral therapy (HAART) and HIV-negative healthy control participants. Reverse transcription-quantitative PCR (RT-qPCR) was conducted to determine the expression levels of genes in peripheral blood mononuclear cells isolated from all participants. The spearman correlation test and linear regression analysis were performed to evaluate the correlation between gene expression level and viral load. The following differentially expressed genes were identified: A20, CYLD, DDX24, MARCH5, MKRN2, PTP1B, RNF125, S1PR1, SOCS1, IFI35, RBCK1, TTLL12 and USP18. The three most differentially expressed genes were A20, S1PR1, and USP18. USP18 correlated positively with viral load. Thirteen immune regulation genes were identified in comparisons of viremic treatment-naïve HIV-positive donors, HAART-treated patients and healthy control participants, indicating the potential of these genes as therapeutic targets. [ABSTRACT FROM AUTHOR]

Abnormal oxidative stress caused by human immunodeficiency virus (HIV) infection affects viral replication and causes non-acquired immune deficiency syndrome-related complications in infected individuals. The transcription factor NFE2-related factor 2 (NRF2), a key regulator of oxidative stress, responds to abnormal oxidative stress by regulating the expression of NRF2-dependent cytoprotective genes. The present study aimed to determine whether inhibition of oxidative stress could control HIV replication and improve cell survival. In this study, the NRF2 activator, methyl bardoxolone, was used to treat cells for HIV infection. The effects on HIV replication and apoptosis pathways were confirmed by NRF2 activation or knockdown . The results showed that NRF2 activation could block HIV replication in macrophages before the integration phase and inhibited the expression of apoptotic pathways in virus-exposed macrophages. The study presents an unconventional anti-viral strategy of activation antioxidant response for HIV infection blocking., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Ltd.)