STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

Abstract

Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

Cytosolic DNA sensor activation inhibits HIV infection of macrophages

“…To survive in the host cells such as macrophages, HIV has evolved the strategies to avoid and/or suppress the intracellular innate immunity. Lima et al showed that STING and cGAS gene expressions were downregulated among HIV‐infected persons after antiretroviral therapy 55 . In addition, a very recent paper demonstrated that through its capsid the pandemic HIV M strain can inhibit cGAS and TRIM5 activation, which results in silent viral replication in myeloid cells 56 .…”

Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α

“…The prevalence of symptoms related to long COVID in the investigated group is described in Table 1. These patients were treated at the outpatient clinic for long COVID at the State University of Pará 25 .…”

“…The concentration of the extracted RNA was determined using a BioDrop™ (Bio-Rad, Hercules, California, USA) according to the manufacturer's instructions. The concentrations of all total RNA samples for synthesis of complementary DNA (cDNA) were equal to 50 ng/µL 25 www.nature.com/scientificreports/…”

“…For the cDNA reaction, a mixture was prepared with a final volume of 20.0 µL containing 2 µL of 10X RT Buffer, 0.8 µL of 25X dNTP Mix (100 nM), 2 µL of random primer, 1 µL of MultiScribe™ Reverse Transcriptase, 1 µL of RNaseOUT™ and 3.2 µL of ultra-pure water provided by the kit as well as 10.0 µL of extracted RNA. The mixture was subjected to cycles of 25 °C for 10 min, 37 °C for 120 min and 85 °C for 5 min using a Mastercycler Personal thermocycler (Eppendorf, Hamburg, Germany) 25 .…”

“…Relative quantification (RQ) of target gene expression was determined using the comparative CT method (∆∆Ct) with the 2-ΔΔCT formula, where ∆∆Ct = ∆Ct sample-∆Ct reference (Life Technologies, Carlsbad, CA, USA) 25 .…”