HIV induced nitric oxide and lipid peroxidation, influences neonatal birthweight in a South African population

Abstract

HIV has been implicated in adverse birth outcomes, due to increased oxidative stress and inflammation. In addition, HIV has been reported to increase nitric oxide levels. Therefore the combined exposures to HIV and traffic-related air pollution, within South Durban, South Africa (SA), may lead to adverse birth outcomes. However, the exact mechanism is still unknown; this study aimed to identify a potential mechanism. First, the influence of HIV on oxidative and nitrosative stress markers in pregnant women was assessed. Secondly, the effect of these stress makers and exposure to oxides of nitrogen (NOx) on neonatal birthweight (BW) was evaluated. Finally, the effect HIV and traffic-related pollution exposure has on the oxidative and endoplasmic profile and epigenetic regulation of Nrf2-Keap1 pathway by miR-144 and miR-28 in pregnant women was determined. Women, in their third trimester with singleton pregnancies, who were HIV+ and HIV-, were recruited from Durban, SA. Biomarker levels of serum nitrites/nitrates (NO) and malondialdehyde (MDA) were analysed and mRNA expression levels of oxidative and endoplasmic stress response genes were assessed. Land regression modelling was performed to determine NOx exposure levels. HIV exposure during pregnancy was associated with increased NO levels. NO was shown to reduce neonatal BW. NO and MDA was found to reciprocally increase each other, with HIV differentially influencing MDA's effect on BW. HIV down-regulated miR-144 which was negatively associated with Nrf2, suggesting a potential mechanism for HIV associated chronic oxidative stress. This study proposes that NO plays a key role in neonatal BW reduction in response to HIV and traffic-related air pollution.

Growth and Neurodevelopment of HIV-Exposed Uninfected Children: a Conceptual Framework

“…HIV infection in adults is associated with an accentuated risk of alcohol and substance use in many settings [34]. Air pollution and environmental toxins (such as mycotoxins) are also potential risk factors for poor child growth [50, 51]. There is some evidence that HIV-infected individuals may have higher mycotoxin levels despite the same exposure when compared to HIV-uninfected controls.…”

“…Mycotoxin exposure may plausibly exacerbate several pathways underlying HIV pathogenesis (including enteropathy and micronutrient deficiencies), thereby affecting early growth [54]. Additionally, the interacting effects of air pollutants and HIV have been associated with adverse birth outcomes, potentially through increasing nitric oxide levels [51].…”

HIV Impairs Alveolar Macrophage Function via MicroRNA-144-Induced Suppression of Nrf2

“…Interestingly, miR-144 appears to mediate influenza-induced lung injury as ablating miR-144 in vivo attenuates influenza replication and lung injury in mice. 41 However, to date, studies connecting HIV-1 and miR-144 have been few and far between, including one recent clinical investigation 42 and our own recent paper on HIV-1-induced epithelial dysfunction. 16 In summary, we determined that HIV-1 infection of human macrophages, or the chronic expression of HIV-1 viral proteins within the alveolar space in a transgenic animal model, induces miR-144.…”

Redox imbalance is related to HIV and pregnancy

“…In a study with healthy pregnant women [ 31 ], MDA concentrations were elevated in the first gestational trimester. In addition, Anderson et al [ 36 ] demonstrated that high levels of MDA influenced the low birth weight of newborns from HIV-positive mothers compared to those without the infection.…”