Epstein-Barr Virus Induces Erosive Arthritis in Humanized Mice

被引：51

作者：

Kuwana, Yoshikazu ^{[1
]}

Takei, Masami ^{[1
]}

Yajima, Misako ^{[2
]}

Imadome, Ken-Ichi ^{[3
]}

Inomata, Hirotake ^{[1
]}

Shiozaki, Masaaki ^{[1
]}

Ikumi, Natsumi ^{[1
]}

Nozaki, Takamasa ^{[1
]}

Shiraiwa, Hidetaka ^{[1
]}

Kitamura, Noboru ^{[1
]}

Takeuchi, Jin ^{[1
]}

Sawada, Shigemasa ^{[1
]}

Yamamoto, Naoki ^{[2
]}

Shimizu, Norio ^{[4
]}

Ito, Mamoru ^{[5
]}

Fujiwara, Shigeyoshi ^{[3
]}

机构：

[1] Nihon Univ, Sch Med, Dept Med, Div Hematol & Rheumatol, Tokyo, Japan

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117595, Singapore

[3] Natl Res Inst Child Hlth & Dev, Dept Infect Dis, Tokyo, Japan

[4] Tokyo Med & Dent Univ, Med Res Inst, Div Med Sci, Dept Virol, Tokyo, Japan

[5] Cent Inst Expt Anim, Kawasaki, Kanagawa, Japan

来源：

PLOS ONE | 2011年 / 6卷 / 10期

关键词：

HUMORAL IMMUNE-RESPONSES; RHEUMATOID-ARTHRITIS; NUCLEAR ANTIGEN; GLYCOPROTEIN GP110; T-CELLS; EPITOPE; CHAIN; LOAD; INFECTION; FREQUENCY;

D O I：

10.1371/journal.pone.0026630

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of rheumatoid arthritis (RA) on the basis of indirect evidence, such as its presence in affected joint tissues, antigenic cross reactions between EBV and human proteins, and elevated humoral and cellular anti-EBV immune responses in patients. Here we report development of erosive arthritis closely resembling RA in humanized mice inoculated with EBV. Human immune system components were reconstituted in mice of the NOD/Shi-scid/IL-2R gamma(null) (NOG) strain by transplantation with CD34(+) hematopoietic stem cells isolated from cord blood. These humanized mice were then inoculated with EBV and examined pathologically for the signs of arthritis. Erosive arthritis accompanied by synovial membrane proliferation, pannus formation, and bone marrow edema developed in fifteen of twenty-three NOG mice transplanted with human HSC and inoculated with EBV, but not in the nine NOG mice that were transplanted with HSC but not inoculated with EBV. This is the first report of an animal model of EBV-induced arthritis and strongly suggest a causative role of the virus in RA.

引用

页数：5

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