Universität zu Köln

Xu, Jianliang, Chikuma, Shunsuke, Hiai, Hiroshi, Kinoshita, Kazuo, Moriya, Kyoji, Koike, Kazuhiko, Marcuzzi, Gian Paolo, Pfister, Herbert, Honjo, Tasuku and Kobayashi, Maki (2014). Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models. Int. Immunol., 26 (7). S. 397 - 407. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2377

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Xu, Jianliang UNSPECIFIED UNSPECIFIED UNSPECIFIED Chikuma, Shunsuke UNSPECIFIED UNSPECIFIED UNSPECIFIED Hiai, Hiroshi UNSPECIFIED UNSPECIFIED UNSPECIFIED Kinoshita, Kazuo UNSPECIFIED UNSPECIFIED UNSPECIFIED Moriya, Kyoji UNSPECIFIED UNSPECIFIED UNSPECIFIED Koike, Kazuhiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Marcuzzi, Gian Paolo UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Honjo, Tasuku UNSPECIFIED UNSPECIFIED UNSPECIFIED Kobayashi, Maki UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-434499
DOI:	10.1093/intimm/dxu040
Journal or Publication Title:	Int. Immunol.
Volume:	26
Number:	7
Page Range:	S. 397 - 407
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2377
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLASS SWITCH RECOMBINATION; CHRONIC HEPATITIS-C; TRANSGENIC MICE; HEPATOCELLULAR-CARCINOMA; CORE PROTEIN; CONSTITUTIVE EXPRESSION; HUMAN HEPATOCYTES; AID; INFECTION; DISEASE Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43449