Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication - PubMed (original) (raw)
Comparative Study
. 2006 Jun;43(6):1364-74.
doi: 10.1002/hep.21187.
Affiliations
- PMID: 16729314
- DOI: 10.1002/hep.21187
Comparative Study
Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication
Marianne Bonvin et al. Hepatology. 2006 Jun.
Abstract
Hypermutations in hepatitis B virus (HBV) DNA by APOBEC3 cytidine deaminases have been detected in vitro and in vivo, and APOBEC3G (A3G) and APOBEC3F (A3F) have been shown to inhibit the replication of HBV in vitro, but the presumably low or even absent hepatic expression of these enzymes has raised the question as to their physiological impact on HBV replication. We show that normal human liver expresses the mRNAs of APOBEC3B (A3B), APOBEC3C (A3C), A3F, and A3G. In primary human hepatocytes, interferon alpha (IFN-alpha) stimulated the expression of these cytidine deaminases up to 14-fold, and the mRNAs of A3G, A3F, and A3B reached expression levels of 10%, 3%, and 3%, respectively, relative to GAPDH mRNA abundance. On transfection, the full-length protein A3B(L) inhibited HBV replication in vitro as efficiently as A3G or A3F, whereas the truncated splice variant A3B(S) and A3C had no effect. A3B(L) and A3B(S) were detected predominantly in the nucleus of uninfected cells; however, in HBV-expressing cells both proteins were found also in the cytoplasm and were associated with HBV viral particles, similarly to A3G and A3F. Moreover, A3G, A3F, and A3B(L), but not A3B(S), induced extensive G-to-A hypermutations in a fraction of the replicated HBV genomes. In conclusion, the editing enzymes A3B(L), A3F, and most markedly A3G, which are expressed in liver and up-regulated by IFN-alpha in hepatocytes, are candidates to contribute to the noncytolytic clearance of HBV.
Similar articles
- Induction of antiviral cytidine deaminases does not explain the inhibition of hepatitis B virus replication by interferons.
Jost S, Turelli P, Mangeat B, Protzer U, Trono D. Jost S, et al. J Virol. 2007 Oct;81(19):10588-96. doi: 10.1128/JVI.02489-06. Epub 2007 Jul 25. J Virol. 2007. PMID: 17652382 Free PMC article. - Cytidine deaminase APOBEC3B interacts with heterogeneous nuclear ribonucleoprotein K and suppresses hepatitis B virus expression.
Zhang W, Zhang X, Tian C, Wang T, Sarkis PT, Fang Y, Zheng S, Yu XF, Xu R. Zhang W, et al. Cell Microbiol. 2008 Jan;10(1):112-21. doi: 10.1111/j.1462-5822.2007.01020.x. Epub 2007 Aug 1. Cell Microbiol. 2008. PMID: 17672864 - Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G.
Rose KM, Marin M, Kozak SL, Kabat D. Rose KM, et al. AIDS Res Hum Retroviruses. 2005 Jul;21(7):611-9. doi: 10.1089/aid.2005.21.611. AIDS Res Hum Retroviruses. 2005. PMID: 16060832 - Hepatitis B: modern concepts in pathogenesis--APOBEC3 cytidine deaminases as effectors in innate immunity against the hepatitis B virus.
Bonvin M, Greeve J. Bonvin M, et al. Curr Opin Infect Dis. 2008 Jun;21(3):298-303. doi: 10.1097/QCO.0b013e3282fe1bb2. Curr Opin Infect Dis. 2008. PMID: 18448976 Review. - The inhibition of hepatitis B virus by APOBEC cytidine deaminases.
Janahi EM, McGarvey MJ. Janahi EM, et al. J Viral Hepat. 2013 Dec;20(12):821-8. doi: 10.1111/jvh.12192. J Viral Hepat. 2013. PMID: 24304451 Review.
Cited by
- APOBEC3B expression in 293T viral producer cells drives mutations in chimeric antigen receptors and reduces CAR T cell efficacy.
Swanson J, Tonne J, Sangsuwannukul T, Thompson J, Kendall B, Liseth O, Metko M, Vile R. Swanson J, et al. Mol Ther Oncol. 2024 Sep 10;32(4):200873. doi: 10.1016/j.omton.2024.200873. eCollection 2024 Dec 19. Mol Ther Oncol. 2024. PMID: 39403625 Free PMC article. - The impact of hepatitis B surface antigen seroconversion on the durability of functional cure induced by pegylated interferon alpha treatment.
Zhang W, Chen J, Sun W, Xie N, Tian F, Ruan Q, Song J. Zhang W, et al. Virol J. 2024 Oct 3;21(1):243. doi: 10.1186/s12985-024-02522-8. Virol J. 2024. PMID: 39363288 Free PMC article. - Intracellular Host Restriction of Hepatitis B Virus Replication.
Sinha P, Thio CL, Balagopal A. Sinha P, et al. Viruses. 2024 May 11;16(5):764. doi: 10.3390/v16050764. Viruses. 2024. PMID: 38793645 Free PMC article. Review. - The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses.
Lovšin N, Gangupam B, Bergant Marušič M. Lovšin N, et al. Pathogens. 2024 Feb 20;13(3):187. doi: 10.3390/pathogens13030187. Pathogens. 2024. PMID: 38535531 Free PMC article. Review. - The Impact of First-Time SARS-CoV-2 Infection on Human Anelloviruses.
Timmerman AL, Commandeur L, Deijs M, Burggraaff MGJM, Lavell AHA, van der Straten K, Tejjani K, van Rijswijk J, van Gils MJ, Sikkens JJ, Bomers MK, van der Hoek L. Timmerman AL, et al. Viruses. 2024 Jan 9;16(1):99. doi: 10.3390/v16010099. Viruses. 2024. PMID: 38257799 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials