2',3'-cyclic nucleotide 3'-phosphodiesterases inhibit hepatitis B virus replication

PLoS One. 2013 Nov 18;8(11):e80769. doi: 10.1371/journal.pone.0080769. eCollection 2013.

Abstract

2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) is a member of the interferon-stimulated genes, which includes isoforms CNP1 and CNP2. CNP1 is locally expressed in the myelin sheath but CNP2 is additionally expressed at low levels outside the nervous system. CNPs regulate multiple cellular functions and suppress protein production by association with polyadenylation of mRNA. Polyadenylation of Hepatitis B virus (HBV) RNAs is crucial for HBV replication. Whether CNPs interact with polyadenylation signal of HBV RNAs and interfere HBV replication is unknown. In this study, we evaluated expressions of CNP isoforms in hepatoma cell lines and their effects on HBV replication. We found that CNP2 is moderately expressed and gently responded to interferon treatment in HepG2, but not in Huh7 cells. The CNP1 and CNP2 potently inhibited HBV production by blocking viral proteins synthesis and reducing viral RNAs, respectively. In chronic hepatitis B patients, CNP was expressed in most of HBV-infected hepatocytes of liver specimens. Knockdown of CNP expression moderately improved viral production in the HepG2.2.15 cells treated with IFN-α. In conclusion, CNP might be a mediator of interferon-induced response against HBV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / genetics*
  • 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / metabolism*
  • Cell Line
  • Gene Expression
  • Gene Knockdown Techniques
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / metabolism
  • Hepatitis B, Chronic / virology
  • Humans
  • Intracellular Space / metabolism
  • Isoenzymes
  • Liver / metabolism
  • Liver / virology
  • Protein Transport
  • Virus Replication*

Substances

  • Isoenzymes
  • 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase

Grants and funding

This study was funded by a grant from National Natural Science Foundation of China (Grand number 30972605), Program for New Century Excellent Talents in University (NCET-11-0011), The Key Project of Beijing Science and Technology Commission (No. D121100003912003) and The National Science and Technology Major Project for Infectious Diseases Control during the 12th Five-Year Plan Period (No. 2012ZX10002003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.