Background Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.Methods We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to evaluate HBV RNA output, including total HBV RNA and 3.5 kb RNA, in order to provide both transcript-pattern and quantitative assessment of transcriptional changes.Results SIRT1 physically interacted with IFI16, with increased colocalization during HBV replication. Both proteins were recruited to HBV cccDNA, promoting transcriptionally active chromatin. Silencing SIRT1 or IFI16 disrupted cccDNA binding and reduced viral RNA levels. Although STING was not cccDNA-associated, its antiviral activity via ISG induction was dependent on IFI16 knockdown produced the strongest reduction in both total HBV RNA and 3.5 kb RNA, supporting a cooperative role for these factors in sustaining HBV transcriptional output. Although STING was not cccDNA-associated, its antiviral activity via ISG induction was dependent on IFI16. Triple knockdown of SIRT1, IFI16, and STING showed the strongest suppression of ISG expression.Conclusion SIRT1 and IFI16 enhance HBV gene expression through epigenetic regulation of cccDNA, while also supporting STING-mediated antiviral responses. These findings reveal a dual regulatory axis governing HBV persistence and identify potential targets for antiviral therapy.
Respiratory syncytial virus (RSV) poses a widespread global burden that typically causes mild, cold-like symptoms in infected healthy adults. However, in vulnerable populations, such as the very young or older adults, RSV infection can lead to severe and potentially fatal disease. Both viral and host factors play a dynamic role in determining disease severity. In the host, dysregulation of both the innate and adaptive immune responses can result in unrestrained viral replication and excessive inflammation. Insight has been gained into the host factors that drive more severe disease following RSV infection using animal models and clinical studies. In this review, we discuss both clinical and in vivo animal model findings to elucidate host immune responses that contribute to disease severity, highlighting pathways that may serve as beneficial therapeutic targets. PubMed, ScienceDirect and Google Scholar were accessed to search for articles up to June 2026. Eligibility criteria included in vitro, in vivo, and clinical studies evaluating the factors associated with RSV disease severity, published in peer-reviewed journals.
