title: Dissection of genetic mechanisms governing the expression of serum retroviral gp70 implicated in murine lupus nephritis.
abstract: 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.
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
authors.forename: Lucie
authors.initials: L
authors.lastname: Baudino
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yoshinobu
authors.forename: Naoki
authors.initials: N
authors.lastname: Morito
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Liliane
authors.initials: L
authors.lastname: Fossati-Jimack
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Morley
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirose
authors.forename: Trine N
authors.initials: TN
authors.lastname: Jørgensen
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Tucker
authors.forename: Christina L
authors.initials: CL
authors.lastname: Roark
authors.forename: Brian L
authors.initials: BL
authors.lastname: Kotzin
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Evans
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D018836:Inflammation Mediators / Q000097:blood / Q000502:physiology; D008181:Lupus Nephritis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001324:Autoantigens; D006023:Glycoproteins; D018836:Inflammation Mediators; D018832:Molecular Chaperones; C479954:Sgp3 protein, mouse; C033589:glycoprotein gp70, murine serum