# Epitranscriptomic regulation of HBV gene expression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $395,000

## Abstract

Project Summary/Abstract
Human hepatitis B virus (HBV causes chronic hepatitis. Chronic hepatitis B is a major risk factor in the
progression to the onset of hepatocellular carcinoma (HCC). In spite of an effective vaccine and currently used
antivirals, there are estimated 350 million infected carriers worldwide. Antivirals do not eliminate HBV DNA in
the nucleus. A better understanding of the role of host and viral factors contributing to chronic hepatitis is
needed. Epitranscriptomic regulation of HBV gene expression provides another layer of regulatory schemes of
gene expression. In this study, we propose to characterize the posttranscriptional modification of viral RNAs at
the N6 position of the adenosine base termed m6A. Our extensive preliminary studies described in the grant
application show that HBV RNAs are methylated as m6A. Using the strategy of silencing of host methylases
and demethylase enzymes involved in epitranscriptomic homeostasis, we present evidence that HBV RNAs
are m6A modified. There was clearly an effect on translation of viral transcripts in the absence of enzyme that
catalyze m6A modification. Our results with MeRIP immunoprecipitation followed by Tru-seq analysis identified
a potential range of sequences enriched in a peak of m6A residues. We mutated about 13 `A' residues in this
region that spans from nucleotides 1700 to 2000 within the HBV genome. These were examined for
translation of HBV proteins and reverse transcription function. Results were striking, in that, the translation was
negatively regulated but reverse transcription was positively regulated by m6A modification. Based on these
exciting data, we propose to continue characterization of m6A modification of HBV RNAs and identify the
functional relevance of this modification in the HBV infection. This study opens a new avenue of HBV research
to investigate epitranscriptomic regulation of the unique HBV life cycle and possible contribution to the
progression to chronicity associated with infection.

## Key facts

- **NIH application ID:** 10361391
- **Project number:** 5R01AI139234-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ALEEM SIDDIQUI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10361391

## Citation

> US National Institutes of Health, RePORTER application 10361391, Epitranscriptomic regulation of HBV gene expression (5R01AI139234-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10361391. Licensed CC0.

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