title: Human parvovirus B19 transgenic mice become susceptible to polyarthritis.
abstract: 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.
authors.affiliation: Department of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Takasawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Munakata
authors.forename: Keiko Kumura
authors.initials: KK
authors.lastname: Ishii
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Minako
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yi
authors.initials: Y
authors.lastname: Fu
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ishii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujii
authors.forename: Takako
authors.initials: T
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takano
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.forename: Misao
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masato
authors.initials: M
authors.lastname: Nose
authors.forename: Suzan
authors.initials: S
authors.lastname: Zolla-Patzner
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
mesh_terms: 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*
chemical_list: D001323:Autoantibodies; D024043:Collagen Type II; C106202:NS1 protein, parvovirus; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins