Identification of human endogenous retroviral antigen and its association with diseases

• Project/Area Number: 03670184
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Tokyo Metropolitan Institute of Gerontology
• Principal Investigator: MARUYAMA Naoki Tokyo Metropolitan Institute of Gerontology Chief, 分子病理部門, 研究室長 (00115940)
• Project Period (FY): 1991 – 1992
• Project Status: Completed (Fiscal Year 1992)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: endogenous retrovirus / recombinant protein / natural antibody / collagen disease / 自然坑体 / 内存性レトロウィルス / 組替え蛋白 / SLE

Research Abstract

To identify the presence of human endogenous retroviral gene product in human tissue, we prepared several recombinant proteins by using gene technology. One of env gene product derived from human endogenous retrovirus like genomic DNA was produced in E. coli. We purified this recombinant protein and immunized to rabbit produce antibody. By using antibody against recombinant env gene product we observed the presence of human endogenous retroviral antigen in the placenta. We detected natural antibody against this protein in the patient sera from systemic lupus erythematosus. Next we prepared recombinant protein using Baculovirus vector system. We modified the genomic DNA encoding gag region of human endogenous retrovirus like DNA by site mutagenesis to produce long-sized openreading frame. By using this modified DNA we obtained recombinat protein corresponding gag protein fo murine of feline leukemia virus. When developing Western hybridization of this recombinant protein with anti-murine leukemia viral p30 serum, the recombinat protein showed strong positivity. These results indicated the origin of human endogenous retrovirus like sequences are derived same origin with murine leukemia virus genome.
Our results may help to understand the association between human endogenous retrovirus and human diseases in future.

Research Products

• [Publications] SHIGEMOTO et al: "Expression and stracture of serum gp 70 as an acute phase protein in NZB micl" Molecular Immunology. 29. 573-582 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] ITOH et al: "Induction of endogenous retroviral gene product(SU) by 1L-6 in murine hepatocytes" clinical and Experimental Immunology. 88. 356-359 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] ITOH,Y et al: "The strain-dependent constitutive expression of murine serum amyloid-P Component is regulated at the transcriptional level." Biochimica et Biophysica Acata. 1131. 261-269 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] FUJITA et al: "Isolation of DNA clone encoding rat senescence marker protein-30(SMP30)and its tissue distribution." Biochimica et Biophysica Acata. 1116. 297-305 (1992)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] KITAMURA et al: "A retinoic acid responsive gene,MK,is preferentially expressed in the proximal tubiles of the kidney and human tumor cell lines" American Journal of Pathology. (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] KITAMIRA et al: "Renal fibroblasts are sensitive to growth -repres- sible and matrix reducible factors from activated lymphocytes" Clinical Experimental Immunology. (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yumura,W., Uchida,K., Sugino,N., Nagasawa,R., Kawashima,A., and Maruyama,N: "The origin of renal amyloidosis in aged mice. Aging" Immunology and Infectious Disease. 3. 117-126 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujita,T., Uchida,K. and Maruyama,N: "Purification of senescence marker protein-30 (SMP30) and its androgen-independent decrease with age in the ratliver" Biochimica et Biophysica Acata. 1116. 122-128 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shigemoto,K., Kubo,S., Itoh,Y., Tate,G., Handa,S. and Maruyama,N: "Expression and structure of serum gp70 as an" acute phase protein in NZB mice. Molecular Immunology. 29. 573-582 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Itoh,Y., Maruyama,N., Kitamura,M., Shirasawa,T., Shigemoto,K. and Koike,T: "Induction of endogenous retroviral gene product (SU) by IL-6in murine hepatocytes" Clinical and Experimental Immunology. 88. 356-359 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kitamura,M., Maruyama,N., Yoshida,H., Nagasawa,R., Mitarai,T. and Sakai,O: "Extracellular matrix contraction by cultured mesangial cells" Modulation by transforming growth factor-b and matrix components. Experimental and Molecular Pathology. 56. 132-143 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Watanabe,K., Nomoto,M., Nagata,S., Itoh,Y., Hikichi,K., Maruyama,N., Mita,T., and Senshu,T: "Rat peptidylarginine deiminase gene : structural analysis and the 5'-flanking sequence" Gene. 114. 261-265 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kitamura,M., Kitamura,A., Mitarai,T., Maruyama,N., Nagasawa,R., Kawamura,T., Yoshida,H., Takahashi,T. and Sakai,O: "Differential gene expression of tissue inhibitor of metaloproteinases (TIMP) and metaloproteinase transin in cultured rat mesangial exposed to high glucose" BBRC. 185. 1048-1054 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Itoh,Y., Takeuchi,S., Shigemoto,K., Kubo,S., Handa,S., Ishikawa,N. and Maruyama,N: "The strain-dependent constitutive expression of murine serum amyloid-P component is regulated at the transcriptional level" Biochimica et Biophysica Acata. 1131. 261-269 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Watanabe,K., Maruyama,N., and Elliott,R.W: "Mapping the mouse Pdi gene to chr4" Mouse Genome. 90. 444-445 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujita,T., Shirasawa,T., Uchida,K. and Maruyama,N: "Isolation of cDNA clone encoding rat senescence marker protein-30 (SMP30) and its tissue distribution" Biochimica et Biophysica Acata. 1116. 297-305 (1992)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kitamura,M., Shirasawa,T., Mitarai,T., Muramatsu,T., and Maruyama,N: "A retinoic acid responsive gene, MK, is preferentially expressed in the proximal tubules of the kidney and human tumor cell lines" American J. Pathology.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kitamura,A., Kitamura,M., Nagasawa,R., Maruyama,N., Mitarai,T., Takahashi,T. and Isoda,K: "Renal fibroblasts are sensitive to growth-repressible and matrix-reducible factors from activated lymphocytes" Clin. Exp.Immunol.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shigemoto et al.: "Expression and structure of serum gp70 as an acute phase protein in NZB mice" Molecular lmmunology. 29. 573-582 (1992)
• [Publications] Itoh et al.: "Induction of endoyenous retroviral gene product(SU)by 1L-6 in murine hepatocytes" Clinical and Experimental Immunology. 88. 356-359 (1992)
• [Publications] Itoh,Y et al.: "The strain-dependent constitutive expression of murine serum amyloid-P component is regulated at the transeriptional level." Biochimica et Biophysica Acata. 1131. 261-269 (1992)
• [Publications] Fujita et al.: "lsolution of cDNA clone encoding rat senescence marker protein-30(SMP30)and its tissue distribution" Biochimica et Biophysica Acata. 1116. 297-305 (1992)
• [Publications] Kitamura et al.: "A retinoic acid responsive gene,MK,is preferentially expressed in the proximal tubules of the kidney and human tumor cell lines" American Journal of Pathology. (1993)
• [Publications] Kitamura et al.: "Renal fibroblasts are sensitive to growth-repressible and matrix reducible fuctors from activated lymphocytes" Clinical and Experimental Immunology. (1993)
• [Publications] Kitamura et al.: "Extracellular matrix contraction by cultured mesangial cells:A new assay system for cell-matrix interaction" Experimental and Molecular pathology.
• [Publications] Fujita Maruyama: "Elevated levels of c-jun and c-fos transcripts in aged rat liver" Biochem,Biophys.Res.Commun.
• [Publications] Shigemoto et al.: "Expression and structure of serum gp70 as an acute phase protein in NZB mice." Molecular Immunology.
• [Publications] Kitamura et al.: "Extracellular matrix coutraction by cultured mesangial cells:Modulation by transforming growth factor-β and matrix components" Experimental and Molecular Pathology.
• [Publications] Itoh et al.: "Induction of ehdogenous retroviral gene product(SU)by IL-6 in murine hepatocytes" Clinical and Experimental Immunology.
• [Publications] Yumura et al.: "The origin of renal amyloidosis in aged mice" Aging:Immunology and Infectious Disease.