Human parvovirus B19 transgenic mice become susceptible to polyarthritis.
Human parvovirus B19 (B19) often causes acute polyarthritis in adults. In this paper, we analyzed nucleotide sequences of the B19 genome of patients with rheumatoid arthritis (RA), and then introduced the nonstructural protein 1 (NS1) gene of B19 into C57BL/6 mice that had a genetic origin not susceptible to arthritis. The transgenic mice developed no lesions spontaneously, but were susceptible to type II collagen (CII)-induced arthritis. B19 NS1 was expressed in synovial cells on the articular lesions that were histologically characteristic of granulomatous synovitis and pannus formation in cartilage and bone. Serum levels of anti-CII Abs and TNF-alpha increased in NS1 transgenic mice to the same levels as those of DBA/1 mice, which were susceptible to polyarthritis. Stimulation with CII increased secretion of Th1-type- and Th2-type cytokines in NS1 transgenic mice, indicating that a nonpermissive H-2(b) haplotype in the wild type of C57BL/6 mice can be made susceptible to polyarthritis through the expression of NS1. This study is the first to show that a viral agent from the joints in humans can cause CII-induced arthritis resembling RA.
Takasawa
Naruhiko
N
Department of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Munakata
Yasuhiko
Y
Ishii
Keiko Kumura
KK
Takahashi
Yuichi
Y
Takahashi
Minako
M
Fu
Yi
Y
Ishii
Tomonori
T
Fujii
Hiroshi
H
Saito
Takako
T
Takano
Hiroshi
H
Noda
Tetsuo
T
Suzuki
Misao
M
Nose
Masato
M
Zolla-Patzner
Suzan
S
Sasaki
Takeshi
T
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000821:virology; D001323:Autoantibodies / Q000097:blood; D001483:Base Sequence; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic / Q000821:virology*; D008969:Molecular Sequence Data; D016732:Parvovirus B19, Human / Q000235:genetics* / Q000276:immunology; D013583:Synovial Membrane / Q000473:pathology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage / Q000235:genetics*
D001323:Autoantibodies; D024043:Collagen Type II; C106202:NS1 protein, parvovirus; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins