Reactivation of human cytomegalovirus inhibits expression of liver fibrosis related cytokines in patients chronically infected with hepatitis C virus genotype 4a

Abstract

BackgroundThe impact of human cytomegalovirus (HCMV) reactivation on the expression pattern of matrix metalloproteinases, their inhibitors and related cytokines during HCV infection poorly understood. MethodsReactivation 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. ResultsChronically 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. ConclusionThe 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.