Alteration of Interspersed Repetitive Sequence Methylation in T Lymphocytes of People Living with HIV: A Preliminary Study

Interspersed repetitive sequence (IRS) consists of various classes. IRS methylation possesses different levels in cell type, cell condition, and pathogenesis of the disease. The current study aimed to evaluate IRS methylation in HIV-1 infected T lymphocytes in patients living with human immunodeficiency virus (HIV) (PLWH). We examined HERV-E LTR2C, HERV-K LTR5Hs, LINE-1, and Alu methylation status in CD4+ T cells and non-CD4+ T cells such as CD8+ T cells of people living with HIV (PLWH) in comparison with healthy donors. Later, we infected peripheral blood mononuclear cells (PBMCs) from healthy donors with HIV-1 and observed methylation level changes of HERV-K and HERV-E for up to 14 days. We found that the methylation of LINE-1 and Alu did not change significantly in either CD4+ or CD8+ T cells. Interestingly, we observed a significant increase in HERV-K methylation and a significant reduction in HERV-E methylation in both cell types. In the HIV-1 infected T lymphocytes experiment, after 4 days, we noticed a reduction in HERV-K methylation and an induction of HERV-E methylation. Nevertheless, there are trends of increased HERV-K methylation and decreased HERV-E methylation on days 7, 10, and 14. The IRS methylation changes were not associated with the HIV-1 quantity. In summary, IRS methylation level was cell type specific. HERV elements methylation had a different pattern in PLWH. The present study provided fundamental knowledge of IRS methylation in T cells of PLWH. The mechanisms and consequences of these virus-associated epigenetic changes should be further investigated.