Cell‐Type‐Specific Expression of Human Endogenous Retroviruses and Epigenetic Regulators in Human Peripheral Blood

Human endogenous retroviruses (HERVs) constitute a substantial fraction of the human genome and are tightly regulated by epigenetic mechanisms. Although HERV transcription has been detected in peripheral blood and shown to vary across immune cell types, including during immune cell differentiation, the contribution of specific circulating blood cell subsets to whole‐blood HERV expression remains insufficiently defined. In this study, we quantified the transcriptional levels of HERV‐H, HERV‐K, and HERV‐W pol genes, together with the epigenetic regulators SETDB1 and TRIM28, in purified peripheral blood mononuclear cells (PBMCs), granulocytes, reticulocytes, and platelets from healthy donors using quantitative real‐time PCR. Gene expression was normalized per 1 × 10 6 cells to allow direct comparison across cell types. HERV transcripts were predominantly detected in leukocytes, whereas reticulocytes and platelets exhibited minimal expression. Within leukocytes, granulocytes displayed significantly higher HERV expression than PBMCs, despite comparable levels of SETDB1 and TRIM28. These findings demonstrate that HERV transcription in peripheral blood is highly cell‐type‐specific and largely attributable to granulocytes, providing a framework for interpreting whole‐blood HERV measurements and highlighting the importance of accounting for blood cell composition in translational studies.