HCMV microRNAs Show Locus-Specific Patterns in Transplant Recipients

Human cytomegalovirus (HCMV) encodes multiple microRNAs that modulate viral replication, immune evasion, and latency, yet how these viral miRNAs relate to their corresponding viral transcripts in infected patients has remained unclear. A new study in BMC Medical Genomics examined three HCMV-encoded microRNAs—miR-UL112-3p, miR-UL22A-3p, and miR-US25-1-3p—together with the viral transcripts UL112, UL22A, and US25 in solid organ transplant recipients, comparing patients with active viral replication against those with no detectable plasma HCMV DNA and healthy controls.

The research team enrolled 30 transplant recipients with plasma HCMV DNA loads above 10,000 copies/mL, designated the active group, and 30 recipients with no detectable plasma HCMV DNA, designated the inactive group, alongside 30 healthy controls. HCMV DNA was quantified using TaqMan real-time PCR, while expression of the UL112, UL22A, and US25 transcripts and their corresponding microRNAs was measured in blood samples by SYBR Green real-time RT-PCR.

The results showed that expression of all three viral transcripts—UL112, UL22A, and US25—was higher in recipients with plasma HCMV DNA loads above 10,000 copies/mL than in recipients with no detectable plasma HCMV DNA and in healthy controls. The microRNA miR-UL112-3p was also elevated in the active infection group, indicating that both viral messenger transcripts and at least one encoded microRNA rise together during high-level plasma viral loads.

Correlation analysis revealed that the relationships between viral transcripts and their microRNAs differ markedly by genomic locus and by infection status. Spearman analysis demonstrated a moderate inverse association between UL112 mRNA and miR-UL112-3p in the inactive HCMV group, with a correlation coefficient of −0.46 and a P value of 0.009, whereas no significant association was observed in the active group, where the coefficient was 0.129 with a P value of 0.49. For the UL22A locus, the transcript and miR-UL22A-3p were not significantly correlated in either group.

In contrast, the US25 locus showed a strikingly different pattern. US25 mRNA and miR-US25-1-3p displayed strong positive correlations in both the inactive group (ρ = 0.92, P < 0.0001) and the active group (ρ = 0.90, P < 0.0001), indicating tight concordance between this viral transcript and its encoded microRNA regardless of plasma DNA status.

The authors conclude that HCMV-encoded microRNAs and their corresponding viral transcripts exhibit locus-specific relationships that differ between groups defined by plasma HCMV DNA status. The inverse association between UL112 and miR-UL112-3p in inactive infection, the absence of correlation for UL22A and miR-UL22A-3p, and the strong concordance between US25 and miR-US25-1-3p indicate that viral miRNA–transcript relationships are not uniform across HCMV loci.

These findings suggest that measuring viral microRNAs alongside viral transcripts could provide a more nuanced picture of HCMV activity in transplant recipients than plasma DNA load alone, although the study was cross-sectional in design and measured associations in blood samples rather than establishing causal mechanisms. Because the miRNA–transcript relationships varied by locus and by whether plasma HCMV DNA was detectable, the results caution against assuming that all HCMV-encoded microRNAs behave similarly during infection. The work, published open access on 29 October 2026, was conducted by Mehdi Golshan, Ramin Yaghobi, Afsoon Afshari, and Bita Geramizadeh, and adds to the evidence that HCMV microRNAs implicated in regulating host antiviral responses and viral persistence show distinct expression patterns in solid organ transplant recipients.

Subject of Research: Expression patterns of HCMV-encoded microRNAs and viral transcripts in solid organ transplant recipients

Article Title: Distinct expression patterns of HCMV-encoded microRNAs and viral transcripts in solid organ transplant recipients

Article References: Golshan, M., Yaghobi, R., Afshari, A., & Geramizadeh, B. (2026). Distinct expression patterns of HCMV-encoded microRNAs and viral transcripts in solid organ transplant recipients. BMC Medical Genomics. https://doi.org/10.1186/s12920-026-02496-2

Image Credits: AI Generated

DOI: 10.1186/s12920-026-02496-2

Keywords: HCMV, microRNAs, solid organ transplant, viral transcripts, UL112, UL22A, US25, real-time PCR, active infection, correlation analysis, BMC Medical Genomics, Distinct