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The following is a summary of “Cobalt chloride-mimicked hepatocyte cell hypoxia induces TREX1 leading to Hepatitis B virus restriction,” published in the January 2025 issue of Infectious Disease by Suspène et al.
Researchers conducted a retrospective study to investigate the role of TREX1, a host restriction enzyme, in inhibiting hepatitis B virus (HBV) replication as part of the intrinsic immune defense.
They generated and modified TREX1-expressing constructs using site-directed mutagenesis. The location and activity of the various TREX1 constructs were assessed by immunofluorescence and FACS. HepaD38 cells were transfected or transduced with the different TREX1 constructs, with or without cobalt chloride-mimicked hypoxia, and released HBV was quantified using qPCR.
The results showed that TREX1 acted as a restriction factor, inhibiting HBV replication. The TREX1 expression increased in response to cobalt chloride, a chemical agent mimicking hypoxia, and reduced HBV replication by a factor of 2 under hypoxic conditions. Additionally, an analysis of 36 HBV-infected individuals with hepatocellular carcinoma revealed an inverse correlation between TREX1 expression and HBV viral load and HBV cccDNA.
Investigators concluded that examining the therapeutic potential of HBV nucleocapsid recycling, engineered to contain the TREX1 enzyme, for degrading both viral and nuclear DNA in infected cells warrants further investigation.
Source: academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiaf002/7943669
