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Updated: May 28, 2026
Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
Epstein-Barr virus induces erosive arthritis in humanized mice
Yoshikazu Kuwana1, Masami Takei, Misako Yajima
1Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Abstract:
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.
Insights
Epstein-Barr virus (EBV) may cause rheumatoid arthritis (RA). Researchers developed a new animal model using humanized mice that developed erosive arthritis after EBV inoculation, suggesting a direct viral link to RA pathogenesis.
Area of Science:
- Immunology
- Virology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) pathogenesis is linked to Epstein-Barr virus (EBV) through indirect evidence.
- Evidence includes EBV presence in joints, antigenic cross-reactivity, and heightened anti-EBV immune responses in RA patients.
Purpose of the Study:
- To investigate the potential causative role of Epstein-Barr virus (EBV) in rheumatoid arthritis (RA) development.
- To establish a novel animal model for studying EBV-induced arthritis.
Main Methods:
- Humanized NOD/Shi-scid/IL-2Rγ(null) (NOG) mice were created by transplanting CD34(+) hematopoietic stem cells (HSCs) from cord blood.
- These humanized mice were inoculated with Epstein-Barr virus (EBV).
- Pathological examination was performed to assess for signs of arthritis.
Main Results:
- Fifteen of twenty-three EBV-inoculated humanized mice developed erosive arthritis.
- The observed arthritis exhibited synovial proliferation, pannus formation, and bone marrow edema, closely resembling human RA.
- Control mice (transplanted with HSCs but not inoculated with EBV) did not develop arthritis.
Conclusions:
- This study presents the first animal model of EBV-induced arthritis.
- The findings strongly suggest a causative role for Epstein-Barr virus (EBV) in the development of rheumatoid arthritis (RA).
