1272 Effects of metal-rich particulate matter exposure on epstein-barr virus and human endogenous retrovirus w (herv-w) methylation healthy steel-workers

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Abstract

Introduction

Inhaled particulate pollutants have been shown to produce systemic changes in DNA methylation. Global hypomethylation has been associated to viral sequence reactivation, possibly linked to the activation of pro-inflammatory pathways occurring after exposure. We aimed at evaluating the effects of PM exposure on DNA methylation of the Wp promoter of the Epstein-Barr Virus (EBV-Wp) and the promoter of the human-endogenous-retrovirus w (HERV-w), chosen as a paradigm of an exogenous virus and an endogenous retroviral sequence, in workers in an electric furnace steel plant with well-characterised exposure to metal-rich particulate matter.

Methods

We measured EBV-Wp and HERV-w DNA methylation through bisulfite PCR Pyrosequencing on peripheral blood leukocytes DNA obtained from 63 male healthy workers, on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (post-exposure). We determined individual exposure to inhalable particles and metals for all subjects. Paired t-test was used to compare baseline and post-exposure samples. Linear mixed models were fitted to evaluate the association between metal-rich particle exposure and DNA methylation.

Results

Comparing samples obtained at baseline and after 3 days of work, the mean methylation of EBV-Wp was significantly higher at baseline compared to post-exposure (baseline=56.7; postexposure=47.9; p-value=0.009), whereas the mean methylation of HERV-w did not significantly differ. In a regression model adjusted for age, body mass index and smoking, nickel, arsenic and lead had a positive association with EBV-Wp methylation (nickel: β=16.16, p-value<0.001; arsenic: β=13.0, p-value=0.02; lead: β=16.53, p-value<0.001).

Conclusions

The difference observed comparing baseline and postexposure samples may be suggestive of a rapid change in EBV methylation induced by air particles, while correlation between EBV methylation and metal exposure may represent an adaptive mechanism that should be further characterised in future investigations.

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