Almeida Giovana W C, Oliveira Martha T, Martines Isabella G L, Fiori Giuliano C, Nevels Michael M, Groves Ian J, Sinclair John, Medina-Pestana José, da Silva Rayra Sampaio, Nakamura Monica, Requião-Moura Lucio, Poole Emma, Silva Maria C Carlan da
Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), São Bernardo do Campo 09606-070, SP, Brazil.
School of Biology, University of St. Andrews, St. Andrews KY16 9ST, UK.
Viruses. 2025 Mar 31;17(4):501. doi: 10.3390/v17040501.
Human cytomegalovirus (HCMV) is a high-risk pathogen in immunocompromised individuals, especially in transplant recipients. HCMV viremia must be monitored, and frequently, patients are treated with antiviral agents. HCMV has a variety of strategies to modulate host antiviral responses, and one important player is a viral homolog of the cellular interleukin-10 (cIL-10). The viral gene produces several HCMV IL-10 transcripts and protein isoforms through alternative splicing. The cmvIL-10 (isoform A) has similar properties to cIL-10, while LAcmvIL-10 (isoform B) has more restricted biological properties. Other isoforms are produced (C to H) but have unknown functions. Here, we investigated the expression of the most abundant transcripts, cmvIL-10 and LAcmvIL-10, in productively and latently infected cells and in peripheral blood mononuclear cells from renal transplant recipients up to 60 days post-transplantation. This study investigated HCMV cmvIL-10 and LAcmvIL-10 transcription profiles in vitro, in productive and latent infection, and in vivo, in peripheral blood mononuclear cells (PBMCs) of renal transplant patients. In vitro, both cmvIL-10 and LAcmvIL-10 transcripts were detected in both types at high levels and low levels in MRC-5 and latent infected (CD14+). When PBMCs from transplant patients were analyzed, LAcmvIL-10 was detected mostly sporadically and in only a few patients, while cmvIL-10 was found in all patients at all time points. Furthermore, it was observed in PBMCs that expression of cmvIL-10 was positively associated with an increase in viral DNA detection in the subsequently collected sample, indicating that expression of cmvIL-10 might precede viral DNA replication. These results contribute to the understanding of HCMV biology in different phases of infection. In addition, our initial analysis suggests that monitoring cmvIL-10, along with viral DNA, could improve early detection of HCMV reactivation in transplant recipients.
人巨细胞病毒（HCMV）是免疫功能低下个体尤其是移植受者中的一种高危病原体。必须监测HCMV病毒血症，并且患者经常接受抗病毒药物治疗。HCMV有多种调节宿主抗病毒反应的策略，其中一个重要因素是细胞白细胞介素-10（cIL-10）的病毒同源物。该病毒基因通过可变剪接产生几种HCMV IL-10转录本和蛋白质异构体。cmvIL-10（异构体A）具有与cIL-10相似的特性，而LAcmvIL-10（异构体B）具有更受限的生物学特性。还产生了其他异构体（C至H），但其功能未知。在此，我们研究了最丰富的转录本cmvIL-10和LAcmvIL-10在有 productive 感染和潜伏感染的细胞以及肾移植受者移植后60天内的外周血单个核细胞中的表达情况。本研究调查了HCMV cmvIL-10和LAcmvIL-10在体外有 productive 感染和潜伏感染时以及在体内肾移植患者外周血单个核细胞（PBMC）中的转录谱。在体外，cmvIL-10和LAcmvIL-10转录本在MRC-5细胞和潜伏感染（CD14 +）细胞中均有高水平和低水平的检测。当分析移植患者的PBMC时，LAcmvIL-10大多是偶尔检测到，且仅在少数患者中检测到，而cmvIL-10在所有患者的所有时间点均能检测到。此外，在PBMC中观察到cmvIL-10的表达与随后采集样本中病毒DNA检测的增加呈正相关，这表明cmvIL-10的表达可能先于病毒DNA复制。这些结果有助于理解HCMV在感染不同阶段的生物学特性。此外，我们的初步分析表明，监测cmvIL-10以及病毒DNA可以改善移植受者中HCMV再激活的早期检测。
