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

Background: The impact of human cytomegalovirus (HCMV) reactivation on the expression pattern of matrix metalloproteinases, their inhibitors and related cytokines during HCV infection poorly understood. Methods: 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 TGF beta 2 and PDGF alpha have been measured by ELISA. Results: Chronically infected HCV patients with reactivated CMV had less expression of TGF-beta 1, TGF-beta 2, PDGF alpha and STAT1 transcripts than HCV patients with latent CMV (p = 0.037, 0.006, 0.001 and 0.009; respectively) and normal controls (TGF-beta 2, p = 0.008). Moreover the expression of (TGF beta 2 and PDGF alpha) 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 TGF beta 2 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. Conclusion: The current data reveal that reactivation of CMV partially blocks the upregulation of 2 important proinflammatory cytokines i.e. TGF beta 2 and PDGF alpha at early stages of fibrosis, moreover this CMV mediated blockage of the STAT1 shows statistical significance at late stage of fibrosis.

Automated summary

The reactivation of CMV in HCV patients affects the expression of certain cytokines and blocks the upregulation of important proinflammatory cytokines in fibrosis, but it does not significantly influence the expression of matrix metalloproteinases and their inhibitors.