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Int Immunol. 2014 Jul;26(7):397-406. doi: 10.1093/intimm/dxu040. Epub 2014 Feb 25.

Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models.

Author information

1
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
2
Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
3
Shiga Medical Center Research Institute, Moriyama, Shiga 524-8524, Japan.
4
Department of Infection Control and Prevention, University of Tokyo, Bunkyo, Tokyo 113-8655, Japan.
5
Department of Gastroenterology, University of Tokyo, Bunkyo, Tokyo 113-8655, Japan.
6
Institute of Virology and Center for Molecular Medicine Cologne, University of Cologne, Cologne D-50931, Germany.
7
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan honjo@mfour.med.kyoto-u.ac.jp.

Abstract

Activation-induced cytidine deaminase (AID) not only promotes immune diversity by initiating somatic hypermutation and class switch recombination in immunoglobulin genes but also provokes genomic instability by introducing translocations and mutations into non-immunoglobulin genes. To test whether AID is essential for virus-induced tumor development, we used two transgenic tumor models: mice expressing hepatitis C virus (HCV) core proteins (HCV-Tg), driven by the hepatitis B virus promoter, and mice expressing human papillomavirus type 8 proteins (HPV8-Tg), driven by the Keratin 14 promoter. Both strains were analyzed in the absence and presence of AID by crossing each with AID (-/-) mice. There was no difference in the liver tumor frequency between the HCV-Tg/AID (+/+) and HCV-Tg/AID (-/-) mice at 20 months of age although the AID (+/+) mice showed more severe histological findings and increased cytokine expression. Furthermore, a low level of AID transcript was detected in the HCV-Tg/AID (+/+) liver tissue that was not derived from hepatocytes themselves but from intra-hepatic immune cells. Although AID may not be the direct cause of HCV-induced oncogenesis, AID expressed in B cells, not in hepatocytes, may prolong steatosis and cause increased lymphocyte infiltration into HCV core protein-induced liver lesions. Similarly, there was no difference in the time course of skin tumor development between the HPV8-Tg/AID (-/-) and HPV8-Tg/AID (+/+) groups. In conclusion, AID does not appear to be required for tumor development in the two virus-induced tumor mouse models tested although AID expressed in infiltrating B cells may promote inflammatory reactions in HCV core protein-induced liver pathogenesis.

KEYWORDS:

hepatitis C virus; human papillomavirus type 8

PMID:
24569264
DOI:
10.1093/intimm/dxu040
[Indexed for MEDLINE]

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