Modulation of hepatitis B virus pregenomic RNA stability and splicing by histone deacetylase 5 enhances viral biosynthesis
PLOS PATHOGENS
Authors: Taha, Taha Y.; Anirudhan, Varada; Limothai, Umaporn; Loeb, Daniel D.; Petukhov, Pavel A.; McLachlan, Alan
Abstract
Hepatitis B virus (HBV) is a worldwide health problem without curative treatments. Investigation of the regulation of HBV biosynthesis by class I and II histone deacetylases (HDACs) demonstrated that catalytically active HDAC5 upregulates HBV biosynthesis. HDAC5 expression increased both the stability and splicing of the HBV 3.5 kb RNA without altering the translational efficiency of the viral pregenomic or spliced 2.2 kb RNAs. Together, these observations point to a broader role of HDAC5 in regulating RNA splicing and transcript stability while specifically identifying a potentially novel approach toward antiviral HBV therapeutic development. Author summary This study demonstrates that HDAC5 deacetylation of host cellular factor(s) results in increased HBV biosynthesis by enhancing viral transcript stability and splicing via direct or indirect binding of host factors to viral intron sequences. This represents the first demonstration of this type of post-transcriptional regulation in the liver and is similar to observations seen for cellular transcripts in neural and cardiac cell types. These observations suggest a more general phenomena which could represent an additional posttranscriptional code governing the regulation of RNA:protein interactions and hence RNA metabolism. Therefore, covalent modifications of RNA binding proteins may modulate post-transcriptional gene expression in an analogous manner to the known histone code that controls gene transcription. Although this analysis primarily relates to the mechanism(s) by which HDAC5 governs HBV RNA metabolism, it does have significant therapeutic implications. The inhibition of HDAC5 in combination with current nucleos(t)ide analog drugs targeting the viral reverse transcriptase/DNA polymerase might aid in the treatment and possible resolution of chronic infections by targeting both host and viral factors.
The perception of people with chronic kidney disease towards exercise and physical activity: a literature review
RENAL SOCIETY OF AUSTRALASIA JOURNAL
Authors: Zhang, Jing; Bennett, Paul N.
Abstract
Background Promoting exercise and physical activity is crucial to people with chronic kidney disease (CKD). This review aims to identify patients' perceived barriers and motivators to facilitate exercise participation. Method English language, peer-reviewed papers published electronically between January 2000 and October 2018 were considered for review. Patients with chronic kidney failure aged 18 years or older were included, but those with acute kidney injury were excluded. Results People with CKD viewed exercise or physical activity as beneficial and believed in their capability of participation. Fatigue, lack of motivation and safety issues were the main barriers identified, whereas internal drive of health improvement or self-efficacy promotion, and the support from family, friends, peers or the healthcare professional were the commonly reported motivators. Conclusion People with CKD want to maintain physical function and understand the importance of exercise. A multidisciplinary team approach is therefore required to maintain effective exercise programmes that promote physical function. Staffing issues and workload need to be evaluated to incorporate an exercise promotion programme into routine clinical practice. Furthermore, involving patients, family and friends in the development of an exercise promotion programme is crucial to ensure both effectiveness and sustainability. Additionally, it was determined that the elderly and those people with less confidence or low self-esteem will need more encouragement and support to promote participation. In summary, an intradialytic exercise (IDE) programme may be possible but needs further research to address its safety issues, and must include the use of technology to provide ongoing support.