학술논문
STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy
stimulator of interferon gene
stimulator of interferon gene
Document Type
Report
Author
de Lima, Lorena Leticia Peixoto; de Oliveira, Allysson Quintino Tenório; Moura, Tuane Carolina Ferreira; da Silva Graça Amoras, Ednelza; Lima, Sandra Souza; da Silva, Andrea Nazaré Monteiro Rangel; Queiroz, Maria Alice Freitas; Cayres-Vallinoto, Izaura Maria Vieira; Ishak, Ricardo; Vallinoto, Antonio Carlos Rosário
Source
Virology Journal. April 15, 2021, Vol. 18 Issue 1
Subject
Language
English
ISSN
1743-422X
Abstract
Author(s): Lorena Leticia Peixoto de Lima[sup.1] , Allysson Quintino Tenório de Oliveira[sup.1] , Tuane Carolina Ferreira Moura[sup.1] , Ednelza da Silva Graça Amoras[sup.1] , Sandra Souza Lima[sup.1] , Andrea Nazaré [...]
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-[alpha] 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.sup.+ and CD8.sup.+ T lymphocyte counts by flow cytometry, and IFN-[alpha] level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4.sup.+ T cell count and the CD4.sup.+/CD8.sup.+ ratio significantly increased (p < 0.0001), the CD8.sup.+ 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-[alpha] did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4.sup.+ 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-[alpha]. The expression of STING and cGAS was not correlated with the plasma level of IFN-[alpha], which suggests that there is another pathway regulating this cytokine in addition to the STING-cGAS pathway. Keywords: STING, CGAS, IFN-[alpha], Expression, HIV-1, ART
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-[alpha] 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.sup.+ and CD8.sup.+ T lymphocyte counts by flow cytometry, and IFN-[alpha] level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4.sup.+ T cell count and the CD4.sup.+/CD8.sup.+ ratio significantly increased (p < 0.0001), the CD8.sup.+ 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-[alpha] did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4.sup.+ 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-[alpha]. The expression of STING and cGAS was not correlated with the plasma level of IFN-[alpha], which suggests that there is another pathway regulating this cytokine in addition to the STING-cGAS pathway. Keywords: STING, CGAS, IFN-[alpha], Expression, HIV-1, ART