Increased HERV-E clone 4-1 mRNA expression was found in SLE CD4+ T-cells and PBMCs, secondary to a variety of factors: activation of Ca++/calcineurin (CaN)/Nuclear factor of activated T cells 1 (NFAT1), due to UVB or foreign infections with high IL6 and TNFα levels; Estrogen receptor-α (ER-α) signaling pathway; abnormal DNA hypomethylation of HERV-E clone 4-1 5’LTR. This evidence concerns the gene ESR1 and systemic lupus erythematosus.