Hepatitis B virus (HBV) causes severe liver disease by establishing persistent infection in human hepatocytes. Current medications suppress viral replication but cannot eliminate the virus from infected cells. Efforts are focused on modulating intracellular immunity to develop new therapies targeting the major genomic form of HBV, known as covalently closed circular DNA (cccDNA). One potential approach involves utilizing cytidine deaminases APOBEC/AID, which have the ability to mutate and degrade HBV cccDNA. Our study reveals a novel evasion strategy used by HBV to counteract APOBEC/AID immunity and maintain a viral reservoir within the nuclei of infected cells by saturating these enzymes with relaxed circular DNA (rcDNA), the primary target of cytidine deaminases. Reducing rcDNA levels by siRNA or lamivudine or by using transcriptionally silenced cccDNA enhances cccDNA deamination by major APOBEC/AID enzymes. We also demonstrate severe deamination of the host genome by APOBEC3A, APOBEC3B, and AID upon viral suppression by siRNA or lamivudine, indicating that APOBEC/AID cannot be regarded as safe for antiviral treatment in cells with low HBV replication levels. Finally, we show that APOBEC3C and APOBEC3H can improve anti-HBV activity of siRNA therapeutics but do not affect cccDNA deamination. Off-site deamination for these factors was not detected at selected cancer-related genes.

Current results do not provide conclusive evidence on the effect of BCG vaccination on COVID-19 alone or in combination with other factors. To address this limitation, in this study we used a citizen science initiative on the COVID-19 pandemic to collect data worldwide during October 2-30, 2020 (1,233 individuals) in a structured way for analyzing factors and characteristics of affected individuals in relation to BCG vaccination. For the first time, the results of our study suggested that vaccination with BCG may increase the risk for COVID-19 at certain age, particularly in individuals vaccinated at childhood. A reasonable explanation for this effect is the activation of certain innate immunity mechanisms associated with inflammatory reactions, which should be considered when analyzing the risks associated with this global pandemic. These factors should be considered when analyzing the risks associated with this global pandemic.