Experimental IgA Nephropathy Induced by Coxsackie B₄ Virus in Mice

Abstract

Viruses have been suspected to be etiological agents of IgA nephropathy. Recently, viruses were detected in renal tissues from patients with IgA nephropathy. We tried to cause lesions similar to IgA nephropathy by inoculating virus into mice and to detect virus RNA in the lesion by in situ hybridization. A group of mice were inoculated intravenously with coxsackie B₄ virus once a month from 1 to 5 months of age and sacrificed monthly from 6 to 12 months of age. Mesangial proliferation and deposits that stained positive with periodic acid-Schiff in light microscopy and electron-dense deposits in electron microscopy were found from 6 months of age. Positive findings for IgG and IgA deposition in the mesangium were noted and the intensity of IgA deposition was predominant after 10 months of age. The signals of coxsackie B₄ virus by in situ hybridization were observed in the lesions. These observations indicate that coxsackie B₄ virus inoculated repeatedly into mice induces lesions similar to IgA nephropathy. The depositions of the lesions may be immune complexes of coxsackie B₄ virus and these immune complexes injure renal tissues.

Experimental Glomerulonephritis following Successive Inoculation of Five Different Serotypes of Group B Coxsackieviruses in Mice

“…However, in the later samples, mesangial proliferation was improved, and the number of PAS-posi tive mesangial deposits decreased. The degree of mesan gial proliferation in this study was similar as compared with that in our previous study of repeated inoculation of CB4 [9], The observational period of mesangial prolifera tion in this study was relatively shorter than that of repeated inoculation of CB4 [9]. No obvious changes in mesangium were found in the control mice.…”

“…myo carditis, and myositis [14]. Moreover, these agents have been reported as the etiological agent in some renal dis eases [1][2][3][4][5][6][7][8][9]. For example, experimental nephritis induced by CB4 was first described by Sun et al [1], subsequent various reports have indicated a relationship of CB4 to renal disease in man and in experimental animals [2-5.…”

“…The role of viruses in the pathogenesis of human renal diseases is not well elucidated, although it can be postulated that in acute infections, viruses may have direct cytopathic effects on the renal tissue, whereas 9], Recently. Yoshida et al [9] obtained similar lesions to human IgA nephropathy, in intravenously inoculated mice with CB4 once a month from 1 to 5 months of age, and demonstrated CB4 viral RNA which were observed in the mesangial lesion using in situ hybridization.…”

Renal Effects of Coxsackie B4 Virus in Hyper-IgA Mice

“…There has been some speculation concerning renal injury by immune complexes (17,19). Immune complexes consist of anti- gen and antibody, and the antigen may be virus or renal tissue that is injured by viral infection.…”

“…The renal tissue specimens were prepared by methods that were described previously by Yoshida et al (19).…”