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Open Access Research article

Fragment of tegument protein pp65 of human cytomegalovirus induces autoantibodies in BALB/c mice

Ao-Ho Hsieh1, Yí-Jyun Jhou2, Chung-Ting Liang3, Mingi Chang4* and Shih-Lien Wang2*

Author Affiliations

1 Institute of Medical Science, Tzu-Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien City, Hualien County 970, Taiwan

2 Institute of Microbiology Immunology and Biochemistry, Tzu-Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien City, Hualien County 970, Taiwan

3 The National Laboratory Animal Center (NLAC), No. 128, Sec. 2, Academia Rd., Nangang Dist., Taipei City 115, Taiwan

4 Development Center of Biotechnology, No.101, Ln. 169, Kangning St., Xizhi Dist, New Taipei City 221, Taiwan

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Arthritis Research & Therapy 2011, 13:R162  doi:10.1186/ar3481


See related editorial by Söderberg-Nauclér, http://arthritis-research.com/content/14/1/101 and related letter by Kim and Kim, http://arthritis-research.com/content/14/5/404

Published: 11 October 2011

Abstract

Introduction

Human cytomegalovirus (HCMV) infection has been implicated in the development of autoimmunity, including systemic lupus erythematosus (SLE). Previously we reported that HCMV phosphoprotein 65 (pp65) could induce early onset of autoantibody and glomerulonephritis on lupus-prone NZB/W mice. This study further examined whether the B cell epitope(s) in pp65 is able to drive the development of autoantibody.

Methods

Sera from SLE patients or HCMVpp65-immunized mice were analyzed for anti-nuclear antibody by immunoblotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescent stain and Crithidia luciliae stain. The deposition of immunoglobulin to the kidney was also examined by immunofluorescent stain. The interactions between pp65 sub-fragment to cellular proteins were revealed by yeast two-hybrid analyses.

Results

Our results showed that most SLE patients possessed antibodies to the C-terminal half of the HCMVpp65 antigen. Of these positive sera, 73% were also positive to the pp65336-439 sub-fragment. The immunization of pp65336-439 induced formation of multiple anti-nuclear antibodies, including anti-chromatin, anti-centriole, anti-mitotic spindle type I/II (MSA I/II) and a significant elevation of anti-double-stranded DNA (anti-dsDNA) antibodies on BALB/c mice. Yeast two-hybrid analyses revealed the binding of pp65336-439 sub-fragment to cellular proteins. Immunoglobulin deposition on glomeruli was also detected on pp65336-439-immunized mice.

Conclusions

Our data suggested that HCMVpp65336-439 sub-fragment may induce cross-reactive antibodies to several nuclear antigens, which could contribute to the development of autoimmunity in genetic-suspected individuals.