Abstract
Human cytomegalovirus (HCMV), a prevalent double-stranded DNA virus, exhibits a high infectioraten, yet the mechanisms underlying latent infection and activation remain unclear. Viral cyclic reactivation in healthy HCMV and latent infection is usually well controlled by the T-cell response. Long noncoding RNA (lncRNA) is known to play vital roles in physiological and pathological processes. This study investigates the impact of T cells on the expression of lncRNA4.9, transforming growth factor-β (TGF-β), and multiple cytokines during HCMV latent infection. We established an HCMV latent infection model, coculturing human acute monocytic leukemia cell line (THP-1) cells with T cells subjected to different treatments: NC1 (THP-1 cells cocultured with untreated T cells), NC2 (HCMV latently infected group without T cells), phytohemagglutinin A (PHA) group (PHA-activated T cells added), FK506 group (FK506-suppressed T cells added), and T-cell group (untreated T cells added). Cytokines were assessed in cell culture supernatants collected at 24, 48, and 72 hours. Reverse transcription-quantitative polymerase chain reaction examined changes in RNA and HCMV DNA copy numbers after 3 and 5 days. In the HCMV latent infection model, PHA group, T-cell group, and FK506 group exhibited significantly increased interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha secretion. Expressions of lncRNA4.9 and TGF-β1 significantly increased in T-cell group after 3 and 5 days. Expressions of lncRNA4.9 and TGF-β1 significantly decreased in the PHA group after 5 days. DNA copy numbers of HCMV decreased in T cell and PHA groups after 3 days, with no significant change after 5 days. This study reveals that PHA-activated T cells downregulate the expression of lncRNA4.9 and TGF-β1 in HCMV, highlighting the effect of T cells on the lncRNA4.9-TGF-β1 axis during HCMV latent infection. Regardless of T-cell activation, the study also indicates that IL-6, IL-10, and tumor necrosis factor-alpha levels increase during HCMV latent infection.