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.

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RESUMOA terapia gênica tem como princípio a transferência de material genético para dentro das células de um indivíduo, com o intuito de corrigir genes responsáveis por características patológicas e, assim, tratar doenças. Desse modo, a entrega eficiente e a expressão apropriada dos genes terapêuticos são requisitos fundamentais para a eficiência da terapia gênica. Diante disso, os vírus se apresentam como importantes sistemas para a transferência de genes, sendo utilizados como uma excelente estratégia para o tratamento de doenças monogênicas e não monogênicas. Os vetores virais baseados em retrovírus, adenovírus, vírus adenoassociados, herpesvírus e poxvírus têm sido estudados para o tratamento de doenças monogênicas, incluindo a doença granulomatosa crônica, a imunodeficiência combinada grave ligada ao X e a deficiência da enzima adenosina desaminase, assim como para as doenças não monogênicas como o câncer. A presente revisão objetiva explorar os aspectos mais relevantes do uso de vetores virais na terapia gênica. Embora sejam eficientes na entrega do material genético, os vetores virais apresentam risco de infecção, ativam a resposta imune do hospedeiro e podem apresentar um potencial oncogênico. Assim, para que a terapia gênica possa ser aplicada na rotina clínica, muitas pesquisas ainda são necessárias para o refinamento e aperfeiçoamento da técnica, incluindo o desenvolvimento dos vetores virais. ABSTRACTThe gene therapy is designed to introduce genetic material into an individual's cells in order to correct genes responsible for pathological features and thus to treat diseases. Thereby, the efficient delivery and the appropriate expression of therapeutic genes are fundamental requirements for the gene therapy efficiency. Accordingly, the viruses are important systems for genes transference and have been used as an excellent strategy in the treatment of monogenic and non-monogenic diseases. The viral vectors based on retroviruses, adenoviruses, adeno-associated viruses, herpesviruses and poxviruses have been studied for the treatment of monogenic diseases, including chronic granulomatous disease, X-linked severe combined immunodeficiency and adenosine deaminase deficiency, as well as non-monogenic diseases such as cancer. This study aims to explore the most relevant aspects of the use of viral vectors in gene therapy. Although they are effective in delivering genetic material, the viral vectors present risk of infection, activate host immune responses and may present oncogenic potential. Thus, for the gene therapy to be applied in the clinical routine, more studies are necessary to improve the technique, including the development of viral vectors.

Full-length dengue virus (DENV) cDNA clones are an invaluable tool for many studies, including those on the development of attenuated or chimeric vaccines and on host-virus interactions. Furthermore, the importance of low passage DENV infectious clones should be highlighted, as these may harbour critical and unique strain-specific viral components from field-circulating isolates. The successful construction of a functional Brazilian low passage DENV serotype 2 full-length clone through homologous recombination reported here supports the use of a strategy that has been shown to be highly useful by our group for the development of flavivirus infectious clones and replicons.