A Review on Inflammasomes and Immune Checkpoints in Pre-Eclampsia Complicated with Tuberculosis and Human Immune Deficiency Virus.

The current review evaluates how inflammasomes and immune checkpoints are regulated in pre-eclampsia (PE) associated with tuberculosis (TB) and Human Immune Deficiency Virus (HIV). Studies indicate that inflammasomes such as (NRLP3, NEK7, and AIM2) and immune checkpoints such as (CLT4, PD-1, TIM3, and LAG-3) are dysregulated in TB- and HIV-infected individuals, and also in pre-eclamptic pregnancies, which explains why pregnant women who are either infected with TB or HIV have an increased risk of developing PE. Evidence suggests that inhibition of inflammasomes and immune checkpoints may assist in the development of novel anti-inflammatory drugs for the prevention and management of PE in patients with or without TB and HIV infection.

Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch.

Understanding the underlying molecular interaction during a therapy switch from lopinavir (LPV) to darunavir (DRV) is essential to achieve long-term virological suppression. We investigated the kinetic and structural characteristics of multidrug-resistant South African HIV-1 subtype C protease (HIV-1 PR) during therapy switch from LPV to DRV using enzyme activity and inhibition assay, fluorescence spectroscopy, and molecular dynamic simulation. The HIV-1 protease variants were from clinical isolates with a combination of drug resistance mutations; MUT-1 (M46I, I54V, V82A, and L10F), MUT-2 (M46I, I54V, L76V, V82A, L10F, and L33F), and MUT-3 (M46I, I54V, L76V, V82A, L90M, and F53L). Enzyme kinetics analysis shows an association between increased relative resistance to LPV and DRV with the progressive decrease in the mutant HIV-1 PR variants' catalytic efficiency. A direct relationship between high-level resistance to LPV and intermediate resistance to DRV with intrinsic changes in the three-dimensional structure of the mutant HIV-1 PR as a function of the multidrug-resistance mutation was observed. In silico analysis attributed these structural adjustments to the multidrug-resistance mutations affecting the LPV and DRV binding landscape. Though DRV showed superiority to LPV, as a lower concentration was needed to inhibit the HIV-1 PR variants, the inherent structural changes resulting from mutations selected during LPV therapy may dynamically shape the DRV treatment outcome after the therapy switch.

Recombinant expression of HIV-1 protease using soluble fusion tags in Escherichia coli: A vital tool for functional characterization of HIV-1 protease.

HIV-1 protease expression in the laboratory is demanding because of its high cytotoxicity, making it difficult to express in bacterial expression systems such as Escherichia coli. To overcome these challenges, HIV-1 protease fusion with solubility enhancing tags helps to mitigate its cytotoxic effect and drive its expression as a soluble protein. Therefore, this review focuses on the expression of bioactive HIV-1 protease using solubility-enhancing fusion tags in Escherichia coli and summarises the characteristic features of the different common fusion tags that have been used in the expression of HIV-1 protease. This review will assist researchers with their choice of protein fusion tag for HIV-1 protease expression.

Serum levels of vasoactive factors in HIV-infected pre-eclamptic women on HAART.

In South Africa, pre-eclampsia (PE) and human immunodeficiency virus (HIV) infection are major causes of pregnancy-related deaths. This study aimed to measure serum levels of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) in HIV-infected highly active antiretroviral therapy (HAART)-treated and HIV-uninfected PE and normotensive women to ascertain if HIV/HAART alters their concentrations. Mean sFlt-1 levels were significantly up-regulated in the PE (HIV-uninfected 4.39 ± 1.29; HIV-infected 5.10 ± 1.10 ng/ml) compared to normotensive women (HIV-uninfected 2.59 ± 0.83; HIV-infected 2.20 ± 0.85 ng/ml). Mean PlGF levels were significantly lower in HIV-uninfected PE vs. HIV-infected normotensive women (29.69 ± 4.47 pg/ml vs. 32.86 ± 6.46 pg/ml; p = .002). In conclusion, PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels. Infection with HIV may have further increased the sFlt-1 levels.IMPACT STATEMENTWhat is already known on this subject? In PE, the numerous identified local and circulating bioactive factors differed in concentrations when compared to normal pregnancy.What do the results of this study add? PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels as well as increased levels of sFlt-1.What are the implications of these findings for clinical practice and/or further research? Understanding the link between PE, HIV and HAART during pregnancy will improve prognosis, management and treatment strategies for women clinically.

The Association of Tuberculosis Mono-infection and Tuberculosis-Human Immunodeficiency Virus (TB-HIV) Co-infection in the Pathogenesis of Hypertensive Disorders of Pregnancy.

PURPOSE OF REVIEW: This review highlights the impact of TB mono-infection and TB-HIV co-infection on the pathogenesis of adverse maternal outcomes such as hypertensive disorders of pregnancy (HDP) and adverse fetal outcomes such as recurrent spontaneous abortion (RSA), fetal growth restriction (FGR), and low birth weight. RECENT FINDINGS: Research has shown that HDP, such as severe pre-eclampsia (PE) and eclampsia, as well as adverse fetal outcomes such as recurrent spontaneous abortion, fetal growth restriction, and low birth weight, are higher in women diagnosed with TB mono-infection and even higher in TB-HIV co-infection compared to those without TB. This is speculated to occur due to exaggerated activation of both angiogenic factors such as vascular endothelial growth factor (VEGF), nitric oxide (NO), angiotensin 2, (Ang 2), intracellular adhesion molecules (ICAMs), and inflammatory cytokines such as interleukin 2 (IL-2), (IL-17), and interferon-gamma (INF-γ). There is a lack of information with regard to the pathogenesis of adverse maternal and fetal outcomes upon TB mono-infection and TB-HIV co-infection; therefore, further investigations on the impact of TB mono-infection and TB-HIV co-infection on adverse maternal and fetal outcomes are urgently needed. This will assist in improving diagnostic procedures in pregnant women affected with TB as wells as TB-HIV co-infection.

Circulating fetal and total cell-free DNA, and sHLA-G in black South African women with gestational hypertension and pre-eclampsia.

OBJECTIVE: Quantification of circulating fetal and total cell-free DNA (cfDNA) and soluble human leucocyte antigen (HLAG) in gestational hypertension and pre-eclampsia. METHODS: Serum cfDNA were quantified in controls, pre-eclamptics, and gestational hypertensive patients using real-time qPCR. Soluble HLAG was measured by enzyme-linked immune-sorbent assay. RESULTS: Serum fetal and total cfDNA levels were higher in pre-eclampsia compared with the controls and gestational hypertensives (p < 0.001), more so in severe compared with mild-to-moderate pre-eclampsia (p < 0.05). Soluble HLAG levels were lower in pre-eclamptics than controls and gestational hypertension (p < 0.05). CONCLUSION: Circulating fetal and total cfDNA were increased, while soluble HLAG was decreased in pre-eclampsia.