Microbial Biotechnology Department, Genetic Engineering Division, National Research Centre, 33 EL Bohouth St. (former El Tahrir St.), Dokki, Giza, 12622, Egypt.
Tropical Medicine Department, Faculty of Medicine, Al-Azhar University, Gouhar Al-Kaed Street, El-Hussein University Hospital, Al-Darasah, Cairo, 11675, Egypt.
Microb Pathog. 2021 Mar;152:104596. doi: 10.1016/j.micpath.2020.104596. Epub 2020 Oct 28.
The impact of human cytomegalovirus (HCMV) reactivation on the expression pattern of matrix metalloproteinases, their inhibitors and related cytokines during HCV infection poorly understood.
Reactivation of CMV in 95 subjects (75 chronically infected HCV patients and 20 healthy subjects) was examined. All studied subjects had detectable IgG antibodies for CMV, but only 35/75 of HCV patients (46.7%) had detectable CMV DNA. The expressions of 11 fibrosis related genes by quantitative real-time PCR were analyzed in subjects' PBMCs. The serum levels of TGFβ2 and PDGFα have been measured by ELISA.
Chronically infected HCV patients with reactivated CMV had less expression of TGF-β1, TGF-β2, PDGFα and STAT1 transcripts than HCV patients with latent CMV (p = 0.037, 0.006, 0.001 and 0.009; respectively) and normal controls (TGF-β2, p = 0.008). Moreover the expression of (TGFβ2 and PDGFα) genes decreased significantly in CMV-reactivated patients during the early stage of fibrosis relative to the comparable stage of HCV infection (p = 0.004 and 0.008; respectively). Besides, the mRNA abundance of STAT1 gene in CMV-reactivated patients decreased dramatically as compared to HCV infections during the late stage of fibrosis (p = 0.014). The TGFβ2 protein level has been declined dramatically in CMV-reactivated patients compared to HCV infected patients and control group (p = 0.001 and 0.033; respectively). Our results suggest that CMV reactivation disrupts the expression of several cytokines as compared to solitary infection with HCV. Noticeably, the expressions of matrix metalloproteinases genes and their inhibitors have not been significantly influenced by reactivation of CMV.
The current data reveal that reactivation of CMV partially blocks the upregulation of 2 important pro-inflammatory cytokines i.e. TGFβ 2 and PDGFα at early stages of fibrosis, moreover this CMV mediated blockage of the STAT1 shows statistical significance at late stage of fibrosis.
人巨细胞病毒（HCMV）的再激活对 HCV 感染期间基质金属蛋白酶、其抑制剂和相关细胞因子表达模式的影响知之甚少。
检测 95 例受试者（75 例慢性 HCV 感染患者和 20 例健康受试者）的 CMV 再激活情况。所有研究对象均检测到针对 CMV 的 IgG 抗体，但仅有 75 例 HCV 患者中的 35 例（46.7%）检测到 CMV DNA。通过定量实时 PCR 分析受试者 PBMC 中 11 种纤维化相关基因的表达。通过 ELISA 测量 TGFβ2 和 PDGFα 的血清水平。
CMV 再激活的慢性 HCV 感染患者的 TGF-β1、TGF-β2、PDGFα 和 STAT1 转录本的表达低于潜伏性 CMV（p=0.037、0.006、0.001 和 0.009；分别）和正常对照（TGF-β2，p=0.008）的表达。此外，CMV 再激活患者在纤维化早期阶段 TGFβ2 和 PDGFα 基因的表达较 HCV 感染时显著降低（p=0.004 和 0.008；分别）。此外，CMV 再激活患者 STAT1 基因的 mRNA 丰度在纤维化晚期与 HCV 感染相比显著降低（p=0.014）。与 HCV 感染患者和对照组相比，CMV 再激活患者的 TGFβ2 蛋白水平显著下降（p=0.001 和 0.033；分别）。我们的结果表明，与单独感染 HCV 相比，CMV 再激活会破坏几种细胞因子的表达。值得注意的是，基质金属蛋白酶基因及其抑制剂的表达不受 CMV 再激活的显著影响。
目前的数据表明，CMV 的再激活在纤维化的早期阶段部分阻断了 2 种重要的促炎细胞因子 TGFβ2 和 PDGFα 的上调，此外，CMV 介导的 STAT1 阻断在纤维化的晚期阶段具有统计学意义。
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