1887

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Volume 83, Issue 1

Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene Free

Abstract

TT virus (TTV) is a newly identified human DNA virus of the family . Its genome consists of six putative open reading frames (ORFs). TTV was isolated originally from a patient with cryptogenic hepatitis and the association of TTV with hepatitis has been studied extensively, while its significance in other diseases is unknown. To examine the pathogenicity of TTV, mice transgenic for the ORF genes in various combinations were produced. A total of 11 independent founder mice was produced: two mice, which were found to carry the ORF1 gene, showed pathological changes in the kidney; other tissues were not affected. In these mice, the transgene was expressed most strongly in the kidney and the transcript was shown to be spliced to encode a protamine-like, highly basic protein. Mice from a line with high transgene expression developed renal failure with severe renal epithelial cell abnormalities resembling those seen in humans with nephrotic syndrome. The transgenic mice with severe ascites died before reaching the age of 5 weeks. Another founder mouse with low expression levels also showed similar, but milder, renal epithelial cell changes, indicating that these effects were not caused by the insertion of the transgene, but, rather, were caused by the ORF1 gene product. These observations suggest that TTV affects renal epithelial cells as part of the naturally occurring infection.

  • Received:
  • Accepted:
  • Published Online:
© Microbiology Society
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/content/journal/jgv/10.1099/0022-1317-83-1-141
2002-01-01
2024-05-02
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References

  1. Allain J. P. 2000; Emerging viral infections relevant to transfusion medicine. Blood Reviews 14:173–181
     [Google Scholar]
  2. Campo N., Brizzolara R., Sinelli N., Torre F., Russo R., Deferrari G., Picciotto A. 2000; TT virus infection in haemodialysis patients. Nephrology Dialysis Transplantation 15:1823–1826
     [Google Scholar]
  3. Chomczynski P., Sacchi N. 1987; Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Analytical Biochemistry 162:156–159
     [Google Scholar]
  4. Farquhar M. G. 1975; The primary glomerular filtration barrier: basement membrane or epithelial slits?. Kidney International 8:197–211
     [Google Scholar]
  5. Gallian P., Berland Y., Olmer M., Raccah D., de Micco P., Biagini P., Simon S., Bouchouareb D., Mourey C., Roubicek C., Touinssi M., Cantaloube J. F., Dussol B., de Lamballerie X. 1999; TT virus infection in French hemodialysis patients: study of prevalence and risk factors. Journal of Clinical Microbiology 37:2538–2542
     [Google Scholar]
  6. Hijikata M., Takahashi K., Mishiro S. 1999; Complete circular DNA genome of a TT virus variant (isolate name SANBAN) and 44 partial ORF2 sequences implicating a great degree of diversity beyond genotypes. Virology 260:17–22
     [Google Scholar]
  7. Horster M. F., Braun G. S., Huber S. M. 1999; Embryonic renal epithelia: induction, nephrogenesis, and cell differentiation. Physiological Reviews 79:1157–1191
     [Google Scholar]
  8. Kamahora T., Hino S., Miyata H. 2000; Three spliced mRNAs of TT virus transcribed from a plasmid containing the entire genome in COS1 cells. Journal of Virology 74:9980–9986
     [Google Scholar]
  9. Kazi A., Miyata H., Kurokawa K., Khan M. A., Kamahora T., Katamine S., Hino S. 2000; High frequency of postnatal transmission of TT virus in infancy. Archives of Virology 145:535–540
     [Google Scholar]
  10. Khudyakov Y. E., Cong M. E., Nichols B., Reed D., Dou X. G., Viazov S. O., Chang J., Fried M. W., Williams I., Bower W., Lambert S., Purdy M., Roggendorf M., Fields H. A. 2000; Sequence heterogeneity of TT virus and closely related viruses. Journal of Virology 74:2990–3000
     [Google Scholar]
  11. Kozak M. 1989; The scanning model for translation: an update. Journal of Cell Biology 108:229–241
     [Google Scholar]
  12. Maggi F., Fornai C., Morrica A., Casula F., Vatteroni M. L., Marchi S., Ciccorossi P., Riente L., Pistello M., Bendinelli M. 1999; High prevalence of TT virus viremia in Italian patients, regardless of age, clinical diagnosis, and previous interferon treatment. Journal of Infectious Diseases 180:838–842
     [Google Scholar]
  13. Mahlknecht U., Hoelzer D. 2000; Histone acetylation modifiers in the pathogenesis of malignant disease. Molecular Medicine 6:623–644
     [Google Scholar]
  14. Martinez N. M., Garcia F., Garcia-Valdecasas J., Bernal C., Garcia F. Jr, Lopez I., Alvarez M., Piedrola G., Maroto M. C. 2000; Prevalence and viral persistence of TT virus in patients on hemodialysis. European Journal of Clinical Microbiology & Infectious Diseases 19:878–880
     [Google Scholar]
  15. Miyata H., Tsunoda H., Kazi A., Yamada A., Khan M. A., Murakami J., Kamahora T., Shiraki K., Hino S. 1999; Identification of a novel GC-rich 113-nucleotide region to complete the circular, single-stranded DNA genome of TT virus, the first human circovirus. Journal of Virology 73:3582–3586
     [Google Scholar]
  16. Nishiguchi S., Enomoto M., Shiomi S., Tanaka M., Fukuda K., Tamori A., Tanaka T., Takeda T., Seki S., Yano Y., Otani S., Kuroki T. 2000; TT virus infection in patients with chronic liver disease of unknown etiology. Journal of Medical Virology 62:392–398
     [Google Scholar]
  17. Nishizawa T., Okamoto H., Konishi K., Yoshizawa H., Miyakawa Y., Mayumi M. 1997; A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochemical and Biophysical Research Communications 241:92–97
     [Google Scholar]
  18. Nishizawa T., Okamoto H., Tsuda F., Aikawa T., Sugai Y., Konishi K., Akahane Y., Ukita M., Tanaka T., Miyakawa Y., Mayumi M. 1999; Quasispecies of TT virus (TTV) with sequence divergence in hypervariable regions of the capsid protein in chronic TTV infection. Journal of Virology 73:9604–9608
     [Google Scholar]
  19. Niwa H., Yamamura K., Miyazaki J. 1991; Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108:193–199
     [Google Scholar]
  20. Okamoto H., Akahane Y., Ukita M., Fukuda M., Tsuda F., Miyakawa Y., Mayumi M. 1998; Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A–G hepatitis. Journal of Medical Virology 56:128–132
     [Google Scholar]
  21. Okamoto H., Takahashi M., Nishizawa T., Ukita M., Fukuda M., Tsuda F., Miyakawa Y., Mayumi M. 1999; Marked genomic heterogeneity and frequent mixed infection of TT virus demonstrated by PCR with primers from coding and noncoding regions. Virology 259:428–436
     [Google Scholar]
  22. Okamoto H., Nishizawa T., Tawara A., Takahashi M., Kishimoto J., Sai T., Sugai Y. 2000a; TT virus mRNAs detected in the bone marrow cells from an infected individual. Biochemical and Biophysical Research Communications 279:700–707
     [Google Scholar]
  23. Okamoto H., Ukita M., Nishizawa T., Kishimoto J., Hoshi Y., Mizuo H., Tanaka T., Miyakawa Y., Mayumi M. 2000b; Circular double-stranded forms of TT virus DNA in the liver. Journal of Virology 74:5161–5167
     [Google Scholar]
  24. Okamura A., Yoshioka M., Kikuta H., Kubota M., Ma X., Hayashi A., Ishiko H., Kobayashi K. 2000; Detection of TT virus sequences in children with liver disease of unknown etiology. Journal of Medical Virology 62:104–108
     [Google Scholar]
  25. Ross R. S., Viazov S., Runde V., Schaefer U. W., Roggendorf M. 1999; Detection of TT virus DNA in specimens other than blood. Journal of Clinical Virology 13:181–184
     [Google Scholar]
  26. Shiffman M. L., Maciewicz R. A., Hu A. W., Howard J. C., Li H. J. 1978; Protein dissociation from DNA in model systems and chromatin. Nucleic Acids Research 5:3409–3426
     [Google Scholar]
  27. Sugiyama K., Goto K., Ando T., Mizutani F., Terabe K., Yokoyama T., Wada Y. 2000; TT virus infection in Japanese children: isolates from genotype 1 are overrepresented in patients with hepatic dysfunction of unknown etiology. Tohoku Journal of Experimental Medicine 191:233–239
     [Google Scholar]
  28. Takahashi K., Iwasa Y., Hijikata M., Mishiro S. 2000; Identification of a new human DNA virus (TTV-like mini virus, TLMV) intermediately related to TT virus and chicken anemia virus. Archives of Virology 145:979–993
     [Google Scholar]
  29. Tuveri R., Jaffredo F., Lunel F., Nalpa B., Pol S., Feray C., Marcellin P., Thibault V., Delagneau J. F., Opolon P., Scarpa B., Brechot C., Thiers V. 2000; Impact of TT virus infection in acute and chronic, viral- and non viral-related liver diseases. Journal of Hepatology 33:121–127
     [Google Scholar]
  30. Wouters-Tyrou D., Chartier-Harlin M. C., Martin-Ponthieu A., Boutillon C., Van Dorsselaer A., Sautiere P. 1991; Cuttlefish spermatid-specific protein T. Molecular characterization of two variants T1 and T2, putative precursors of sperm protamine variants Sp1 and Sp2. Journal of Biological Chemistry 266:17388–17395
     [Google Scholar]
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Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene
J. Gen. Virol. 83, 141 (2002); https://doi.org/10.1099/0022-1317-83-1-141
/content/journal/jgv/10.1099/0022-1317-83-1-141
/content/journal/jgv/10.1099/0022-1317-83-1-141
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