Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis.

Jean Pierre Vartanian, Michel Henry, Agnès Marchio, Rodolphe Suspène, Marie Ming Aynaud, Denise Guétard, Minerva Cervantes-Gonzalez, Carlo Battiston, Vincenzo Mazzaferro, Pascal Pineau, Anne Dejean, Simon Wain-Hobson

Research output: Contribution to journalArticle

Abstract

DNA viruses, retroviruses and hepadnaviruses, such as hepatitis B virus (HBV), are vulnerable to genetic editing of single stranded DNA by host cell APOBEC3 (A3) cytidine deaminases. At least three A3 genes are up regulated by interferon-alpha in human hepatocytes while ectopic expression of activation induced deaminase (AICDA), an A3 paralog, has been noted in a variety of chronic inflammatory syndromes including hepatitis C virus infection. Yet virtually all studies of HBV editing have confined themselves to analyses of virions from culture supernatants or serum where the frequency of edited genomes is generally low (<or = 10(-2)). We decided to look at the nature and frequency of HBV editing in cirrhotic samples taken during removal of a primary hepatocellular carcinoma. Forty-one cirrhotic tissue samples (10 alcoholic, 10 HBV(+), 11 HBV(+)HCV(+) and 10 HCV(+)) as well as 4 normal livers were studied. Compared to normal liver, 5/7 APOBEC3 genes were significantly up regulated in the order: HCV+/-HBV>HBV>alcoholic cirrhosis. A3C and A3D were up regulated for all groups while the interferon inducible A3G was over expressed in virus associated cirrhosis, as was AICDA in approximately 50% of these HBV/HCV samples. While AICDA can indeed edit HBV DNA ex vivo, A3G is the dominant deaminase in vivo with up to 35% of HBV genomes being edited. Despite these highly deleterious mutant spectra, a small fraction of genomes survive and contribute to loss of HBeAg antigenemia and possibly HBsAg immune escape. In conclusion, the cytokine storm associated with chronic inflammatory responses to HBV and HCV clearly up regulates a number of A3 genes with A3G clearly being a major restriction factor for HBV. Although the mutant spectrum resulting from A3 editing is highly deleterious, a very small part, notably the lightly edited genomes, might help the virus evolve and even escape immune responses.

Original languageEnglish
Article numbere1000928
JournalPLoS Pathogens
Volume6
Issue number5
Publication statusPublished - May 2010

Fingerprint

Viral DNA
Hepatitis B
Hepatitis B virus
Fibrosis
Genome
Hepadnaviridae
Cytidine Deaminase
Viruses
Alcoholic Liver Cirrhosis
DNA Viruses
Hepatitis B e Antigens
Single-Stranded DNA
Virus Diseases
Retroviridae
Hepatitis B Surface Antigens
Interferon-alpha
Hepacivirus
Virion
Interferons
Genes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Vartanian, J. P., Henry, M., Marchio, A., Suspène, R., Aynaud, M. M., Guétard, D., ... Wain-Hobson, S. (2010). Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. PLoS Pathogens, 6(5), [e1000928].

Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. / Vartanian, Jean Pierre; Henry, Michel; Marchio, Agnès; Suspène, Rodolphe; Aynaud, Marie Ming; Guétard, Denise; Cervantes-Gonzalez, Minerva; Battiston, Carlo; Mazzaferro, Vincenzo; Pineau, Pascal; Dejean, Anne; Wain-Hobson, Simon.

In: PLoS Pathogens, Vol. 6, No. 5, e1000928, 05.2010.

Research output: Contribution to journalArticle

Vartanian, JP, Henry, M, Marchio, A, Suspène, R, Aynaud, MM, Guétard, D, Cervantes-Gonzalez, M, Battiston, C, Mazzaferro, V, Pineau, P, Dejean, A & Wain-Hobson, S 2010, 'Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis.', PLoS Pathogens, vol. 6, no. 5, e1000928.
Vartanian JP, Henry M, Marchio A, Suspène R, Aynaud MM, Guétard D et al. Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. PLoS Pathogens. 2010 May;6(5). e1000928.
Vartanian, Jean Pierre ; Henry, Michel ; Marchio, Agnès ; Suspène, Rodolphe ; Aynaud, Marie Ming ; Guétard, Denise ; Cervantes-Gonzalez, Minerva ; Battiston, Carlo ; Mazzaferro, Vincenzo ; Pineau, Pascal ; Dejean, Anne ; Wain-Hobson, Simon. / Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. In: PLoS Pathogens. 2010 ; Vol. 6, No. 5.
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