Epstein-Barr virus induces erosive arthritis in humanized mice.
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-2Rγ(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.
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Yoshikazu
Y
Kuwana
Masami
M
Takei
Misako
M
Yajima
Ken-ichi
K
Imadome
Hirotake
H
Inomata
Masaaki
M
Shiozaki
Natsumi
N
Ikumi
Takamasa
T
Nozaki
Hidetaka
H
Shiraiwa
Noboru
N
Kitamura
Jin
J
Takeuchi
Shigemasa
S
Sawada
Naoki
N
Yamamoto
Norio
N
Shimizu
Mamoru
M
Ito
Shigeyoshi
S
Fujiwara
D000818:Animals; D001168:Arthritis / Q000473:pathology* / Q000821:virology*; D001853:Bone Marrow / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D007596:Joints / Q000473:pathology / Q000821:virology; D051379:Mice