Correction for Patro et al., Shift in Monocyte Apoptosis with Increasing Viral Load and Change in Apoptosis-Related ISG/Bcl2 Family Gene Expression in Chronically HIV-1-Infected Subjects

ABSTRACTAlthough monocytes and macrophages are targets of HIV-1-mediated immunopathology, the impact of high viremia on activation-induced monocyte apoptosis relative to monocyte and macrophage activation changes remains undetermined. In this study, we determined constitutive and oxidative stress-induced monocyte apoptosis in uninfected and HIV+individuals across a spectrum of viral loads (n =35; range, 2,243 to 1,355,998 HIV-1 RNA copies/ml) and CD4 counts (range, 26 to 801 cells/mm3). Both constitutive apoptosis and oxidative stress-induced apoptosis were positively associated with viral load and negatively associated with CD4, with an elevation in apoptosis occurring in patients with more than 40,000 (4.6 log) copies/ml. As expected, expression of Rb1 and interferon-stimulated genes (ISGs), plasma soluble CD163 (sCD163) concentration, and the proportion of CD14++CD16+intermediate monocytes were elevated in viremic patients compared to those in uninfected controls. Although CD14++CD16+frequencies, sCD14, sCD163, and most ISG expression were not directly associated with a change in apoptosis, sCD14 and ISG expression showed an association with increasing viral load. Multivariable analysis of clinical values and monocyte gene expression identified changes in IFI27, IFITM2, Rb1, and Bcl2 expression as determinants of constitutive apoptosis (P= 3.77 × 10−5; adjustedR2= 0.5983), while changes in viral load, IFITM2, Rb1, and Bax expression were determinants of oxidative stress-induced apoptosis (P= 5.59 × 10−5; adjustedR2= 0.5996). Our data demonstrate differential activation states in monocytes between levels of viremia in association with differences in apoptosis that may contribute to greater monocyte turnover with high viremia.IMPORTANCEThis study characterized differential monocyte activation, apoptosis, and apoptosis-related gene expression in low- versus high-level viremic HIV-1 patients, suggesting a shift in apoptosis regulation that may be associated with disease state. Using single and multivariable analysis of monocyte activation parameters and gene expression, we supported the hypothesis that monocyte apoptosis in HIV disease is a reflection of viremia and activation state with contributions from gene expression changes within the ISG and Bcl2 gene families. Understanding monocyte apoptosis response may inform HIV immunopathogenesis, retention of infected macrophages, and monocyte turnover in low- or high-viral-load states.

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

Virology Journal ◽

10.1186/s12985-021-01548-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Lorena Leticia Peixoto de Lima ◽

Allysson Quintino Tenório de Oliveira ◽

Tuane Carolina Ferreira Moura ◽

Ednelza da Silva Graça Amoras ◽

Sandra Souza Lima ◽

...

Keyword(s):

Gene Expression ◽

Viral Load ◽

T Cell ◽

Antiretroviral Therapy ◽

Cell Count ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Α Level ◽

The Impact ◽

Hiv 1

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.

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Evaluation of the expression pattern of 4 microRNAs and their correlation with cellular/viral factors in PBMCs of Long Term non-progressors and HIV infected naïve Individuals

Current HIV Research ◽

10.2174/1570162x19666210906143136 ◽

2021 ◽

Vol 19 ◽

Author(s):

Sogol Jamshidi ◽

Farah Bokharaei-Salim ◽

Javid Sadri Nahand ◽

Seyed Hamidreza Monavari ◽

Mohsen Moghoofei ◽

...

Keyword(s):

Gene Expression ◽

Viral Load ◽

T Cell ◽

Cell Count ◽

Expression Pattern ◽

Cd4 T Cell ◽

Mirnas Expression ◽

Hiv 1 ◽

Cd4 T Cell Count

Background: Long-term non-progressors (LTNPs) are small subsets of HIV-infected subjects that can control HIV-1 replication for several years without receiving ART. The exact mechanism of HIV-1 suppression has not yet been completely elucidated. Although the modulatory role of microRNAs (miRNAs) in HIV-1 replication has been reported, their importance in LTNPs is unclear. Objective: The aim of this cross-sectional study was to assess the expression pattern of miR-27b, -29, -150, and -221, as well as their relationship with CD4+ T-cell count, HIV-1 viral load, and nef gene expression in peripheral blood mononuclear cells (PBMCs) of untreated viremic patients and in LTNPs. Methods: MiRNAs expression levels were evaluated with real-time PCR assay using RNA isolated from PBMCs of LTNPs, HIV-1 infected naive patients, and healthy people. Moreover, CD4 T-cell count, HIV viral load, and nef gene expression were assessed. Results: The expression level of all miRNAs significantly decreased in the HIV-1 patient group compared to the control group, while the expression pattern of miRNAs in the LNTPs group was similar to that in the healthy subject group. In addition, there were significant correlations between some miRNA expression with viral load, CD4+ T-cell count, and nef gene expression. Conclusion: The significant similarity and difference of the miRNA expression pattern between LNTPs and healthy individuals as well as between elite controllers and HIV-infected patients, respectively, showed that these miRNAs could be used as diagnostic biomarkers. Further, positive and negative correlations between miRNAs expression and viral/cellular factors could justify the role of these miRNAs in HIV-1 disease monitoring.

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STING and cGAS Gene Expressions Were Downregulated Among HIV-1-Infected Persons After Antiretroviral Therapy

10.21203/rs.3.rs-248345/v1 ◽

2021 ◽

Author(s):

Lorena Letícia Peixoto de Lima ◽

Allysson Quintino Tenório de Oliveira ◽

Tuane Carolina Ferreira Moura ◽

Ednelza da Silva Graça Amoras ◽

Sandra Souza Lima ◽

...

Keyword(s):

Gene Expression ◽

Viral Load ◽

T Cell ◽

Antiretroviral Therapy ◽

Cell Count ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Α Level ◽

The Impact ◽

Hiv 1

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.

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