There are hundreds of millions of sufferers worldwide, and effective treatment options suppress HBV replication and prevent liver disease progression. Since the immune system does not clear HBV, in most cases viral replication rebounds upon cessation of therapy. Interferon alpha (IFNα) is an alternative therapy for chronic HBV infection, which however suffers from low response rates and frequent side effects. Therefore, new and alternative treatment approaches are necessary for controlling HBV infections. The scientific scope of the EU-funded NAVICHEB (New advanced vaccines in chronic hepatitis B) project was to develop murine models for studying the molecular mechanisms of HBV infection. Such preclinical tools are essential for dissecting disease pathogenesis and developing new therapeutic approaches. Since HBV does not naturally infect mice, researchers successfully introduced the genome of HBV into hepatocytes using a recombinant adeno-associated vector serotype 8. The established model of chronic HBV infection was then used towards the development of novel treatment strategies. Using different inducers of the IFN type I pathway in the liver, the research teams wished to concentrate the cytokine to the target organ and reduce systemic side effects observed with the administration of recombinant IFNα. They observed that the inducers interfered with viral replication, clearly indicating that HBV escapes immune activation and attack. Further insight into HBV immune evasion, unveiled a mechanism that stimulates the expression of alternative spliced forms of STING, an intracellular pathogen sensor. Scientists discovered that these alternative forms inhibit normal STING function and prevent antiviral responses. Overall, the activities of the NAVICHEB study led to invaluable preclinical tools for studying and elucidating the mechanism of HBV infection. The identification of putative new HBV targets opens up new avenues for fighting chronic infection.
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