hsa-miR-181-5p inhibits human immunodeficiency virus type 1 replication by downregulating DDX3X expression.

BACKGROUND: HIV-1 infection affects expression profiles of microRNA. miR-181 is found negatively correlated with HIV-1 viral load. This study aimed to explain that miR-181 targets DDX3X, a host factor involved in HIV-1 nuclear export, thereby inhibiting HIV-1 replication. METHODS: To verify our hypothesis, first, the relationship between miR-181 expression, DDX3X expression, and HIV-1 viral load was analyzed. Second, miR-181 mimics were transfected into Jurkat cells infected with wild pNL4-3 strain or H9-IIIB cells with HIV-1 replication-competent for HIV-1 viral protein P24(Gag) detection. Besides the reporter gene plasmid containing the DDX3X mRNA sequence was transfected into 293T cells to demonstrate the targeting of miR-181 to the DDX3X mRNA. Finally, the spliced, unspliced, or incompletely spliced HIV-1 transcripts and HIV-1 Tat, Rev, and Gag mRNA were also detected after miR-181 transfection. RESULTS: Our result proved that miR-181 significantly reduced the HIV-1 viral protein Gag(P24) level and targeted DDX3X mRNA 3'-UTR, inhibiting the unspliced or incompletely spliced HIV-1 mRNA's nuclear export. CONCLUSION: Our results confirmed that miR-181 is involved in HIV-1 viral replication in lymphocytes by downregulating DDX3X expression. The research provides a research basis for future HIV-1 antiviral research.

Increased Microbial Translocation is a Prognostic Biomarker of Different Immune Responses to ART in People Living with HIV.

Background: Microbial translocation (MT) is a characteristic of human immunodeficiency virus (HIV) infection. Whether MT is also a biomarker of different immune responses to antiretroviral therapy (ART) received by people living with HIV (PLWH) is not known. Methods: We examined the presence of MT in a cohort of 33 HIV-infected immunological responders (IRs) and 28 immunological non-responders (INRs) (≥500 and <200 cluster of differentiation (CD)4+ T-cell counts/µL after 2 years of HIV-1 suppression, respectively) with no comorbidities. Plasma samples were used to measure the circulating levels of MT markers. All enrolled study participants had received 2 years of viral-suppression therapy. Results: Levels of lipopolysaccharide (P = 0.0185), LPS-binding protein (P < 0.0001), soluble-CD14 (P < 0.0001), and endogenous endotoxin-core antibody (P < 0.0001) at baseline were significantly higher in INRs than in IRs and were associated with an increased risk of an immunological non-response, whereas the level of intestinal fatty acid-binding protein did not show this association. Analysis of receiver operating characteristic (ROC) curves demonstrated the utility of these individual microbial markers in discriminating INRs after ART in people living with HIV with high sensitivity, specificity, and area under the ROC curve. Conclusion: INRs in HIV infection are characterized by increased MT at baseline. These markers could be used as a rapid prognostic tool for predicting immune responses in people infected with the HIV.

Global, regional, and national HIV/AIDS disease burden levels and trends in 1990-2019: A systematic analysis for the global burden of disease 2019 study.

Background: Since the first HIV/AIDS case appeared in 1980s, HIV/AIDS has been the focus of international attention. As a major public health problem, there are epidemiological uncertainties about the future of HIV/AIDS. It is important to monitor the global statistics of HIV/AIDS prevalence, deaths, disability adjusted life years (DALYs), and risk factors for adequate prevention and control. Methods: The Global Burden of Disease Study 2019 database was used to analyze the burden of HIV/AIDS in 1990-2019. By extracting global, regional, and national data on HIV/AIDS prevalence, deaths, and DALYs, we described the distribution by age and sex, explored the risk factors, and analyzed the trends in HIV/AIDS. Results: In 2019, there were 36.85 million HIV/AIDS cases (95% UI: 35.15-38.86 million), 863.84 thousand deaths (95% UI: 78.61-99.60 thousand), and 47.63 million (95% UI: 42.63-55.65 million) DALYs. The global age-standardized HIV/AIDS prevalence, death, and DALY rates were 454.32 (95% UI: 433.76-478.59), 10.72 (95% UI: 9.70-12.39), and 601.49 (95% UI: 536.16-703.92) per 100,000 cases, respectively. In 2019, the global age-standardized HIV/AIDS prevalence, death, and DALY rates increased by 307.26 (95% UI: 304.45-312.63), 4.34 (95% UI: 3.78-4.90), and 221.91 (95% UI: 204.36-239.47) per 100,000 cases, respectively, compared to 1990. Age-standardized prevalence, death, and DALY rates decreased in high sociodemographic index (SDI) areas. High age-standardized rates were observed in low sociodemographic index areas, while low age-standardized rates were observed in high sociodemographic index areas. In 2019, the high age-standardized prevalence, death, and DALY rates were predominant in Southern Sub-Saharan Africa, and global DALYs peaked in 2004 and subsequently decreased. The highest global HIV/AIDS DALYs were in the 40-44 age group. The main risk factors affecting HIV/AIDS DALY rates included behavioral risks, drug use, partner violence, and unsafe sex. Conclusions: HIV/AIDS disease burden and risk factors vary by region, sex, and age. As access to health care increases across countries and treatment for HIV/AIDS infection improves, the HIV/AIDS disease burden is concentrated in areas with low SDIs, particularly in South Africa. Regional differences should be fully considered to target optimal prevention strategies and treatment options based on risk factors.

Activation of NRF2 blocks HIV replication and apoptosis in macrophages.

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.