Hepatitis B virus polymerase restricts LINE-1 mobility

Gene. 2023 Jan 20:850:146943. doi: 10.1016/j.gene.2022.146943. Epub 2022 Oct 2.

Abstract

Long interspersed element-1 (LINE-1, L1) transposable element (TE) composes about 17% of the human genome. However, genetic and biochemical interactions between L1 and hepatitis B virus (HBV) remain poorly understood. In this study, I found that HBV restricts L1 retrotransposition in a reverse transcriptase (RT)-independent manner. Notably, HBV polymerase (Pol) strongly inhibited L1 retrotransposition. Indeed, the ribonuclease H (RNase H) domain was essential for inhibition of L1 retrotransposition. The L1 ORF1p RNA-binding protein predominantly localized into cytoplasmic RNA granule termed P-body. However, HBV Pol hijacked L1 ORF1p from P-body through an interaction with L1 ORF1p, when both proteins were co-expressed. Furthermore, HBV Pol repressed the L1 5' untranslated region (UTR). Altogether, HBV seems to restrict L1 mobility at multiple steps. Thus, these results suggest a novel function or activity of HBV Pol in regulation of L1 retrotransposition.

Keywords: HBV; LINE-1; Polymerase; RNase H; Retrotransposition; Reverse transcription.

MeSH terms

  • 5' Untranslated Regions
  • DNA Transposable Elements* / genetics
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / metabolism
  • Humans
  • Long Interspersed Nucleotide Elements* / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Directed DNA Polymerase* / genetics
  • RNA-Directed DNA Polymerase* / metabolism
  • Ribonuclease H / genetics
  • Ribonuclease H / metabolism

Substances

  • 5' Untranslated Regions
  • DNA Transposable Elements
  • Ribonuclease H
  • RNA-Binding Proteins
  • RNA-Directed DNA Polymerase
  • P protein, Hepatitis B virus