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* Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland;
Molecular Genetics and Rheumatology Section, Imperial College London, London, United Kingdom;
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan;
Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and
¶ Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840
The endogenous retroviral envelope glycoprotein, gp70, implicated in murine lupus nephritis is secreted by hepatocytes as an acute phase protein, and it has been thought to be a product of an endogenous xenotropic virus, NZB-X1. However, since endogenous polytropic (PT) and modified polytropic (mPT) viruses encode gp70s that are closely related to xenotropic gp70, these viruses can be additional sources of serum gp70. To better understand the genetic basis of the expression of serum gp70, we analyzed the abundance of xenotropic, PT, or mPT gp70 RNAs in livers and the genomic composition of corresponding proviruses in various strains of mice, including two different Sgp (serum gp70 production) congenic mice. Our results demonstrated that the expression of different viral gp70 RNAs was remarkably heterogeneous among various mouse strains and that the level of serum gp70 production was regulated by multiple structural and regulatory genes. Additionally, a significant contribution of PT and mPT gp70s to serum gp70 was revealed by the detection of PT and mPT, but not xenotropic transcripts in 129 mice, and by a closer correlation of serum levels of gp70 with the abundance of PT and mPT gp70 RNAs than with that of xenotropic gp70 RNA in Sgp3 congenic mice. Furthermore, the injection of lipopolysaccharides selectively up-regulated the expression of xenotropic and mPT gp70 RNAs, but not PT gp70 RNA. Our data indicate that the genetic origin of serum gp70 is more heterogeneous than previously thought, and that distinct retroviral gp70s are differentially regulated in physiological vs inflammatory conditions.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant from the Swiss National Foundation for Scientific Research. L.H.E. was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
2 L.B., K.Y., and N.M. contributed equally to this work.
3 Current address: Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA 91320.
4 Address correspondence and reprint requests to Dr. Shozo Izui, Department of Pathology and Immunology, Centre Médical Universitaire, 1211 Geneva 4, Switzerland. E-mail address: Shozo.Izui{at}medecine.unige.ch
5 Abbreviations used in this paper: SLE, systemic lupus erythematosus; gp70 IC, gp70-anti-gp70 immune complexes; B6, C57BL/6; B10, C57BL/10; PT, polytropic; mPT, modified PT; TBP, TATA-binding protein; VRA, hypervariable region A; IL6-RE, IL-6-responsive element.
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