Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis.
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 activat...
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2010
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oai:doaj.org-article:5240a683b4e14ce6945373475f9c8d052021-12-02T20:00:38ZMassive APOBEC3 editing of hepatitis B viral DNA in cirrhosis.1553-73661553-737410.1371/journal.ppat.1000928https://doaj.org/article/5240a683b4e14ce6945373475f9c8d052010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20523896/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374DNA 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.Jean-Pierre VartanianMichel HenryAgnès MarchioRodolphe SuspèneMarie-Ming AynaudDenise GuétardMinerva Cervantes-GonzalezCarlo BattistonVincenzo MazzaferroPascal PineauAnne DejeanSimon Wain-HobsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 5, p e1000928 (2010) |
| institution |
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| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 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 Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Jean-Pierre Vartanian |
| title |
Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. |
| title_short |
Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. |
| title_full |
Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. |
| title_fullStr |
Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. |
| title_full_unstemmed |
Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis. |
| title_sort |
massive apobec3 editing of hepatitis b viral dna in cirrhosis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/5240a683b4e14ce6945373475f9c8d05 |
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