Skip to main content

Advertisement

SpringerLink
Log in

Analysis of bovine foamy virus btas mRNA transcripts during persistent infection

  • Published:
Virus Genes Aims and scope Submit manuscript

Abstract

Foamy virus (FV) is an unconventional retrovirus that possesses a complex genome and a special mechanism for gene expression regulation. The genome encodes transcriptional protein Tas which is found to regulate both the internal promoter (IP) and the long terminal repeat promoter (LTR). However, the detailed mechanism of Tas-mediated gene expression remains unknown. In this study, we provided the first evidence for the temporal production and utilization of four different bovine foamy virus (BFV) btas mRNAs during persistent infection. These four forms of btas mRNA transcripts initiated either at BFV LTR or IP and spliced or unspliced have a differential ability to activate BFV promoters. Furthermore, by developing an MS2 translational operator/coat protein combined system to track mRNA exportation from the nucleus and distribution throughout the cytoplasm, we observed that the IP spliced transcript could be exported into the cytoplasm more efficiently than unspliced transcripts. These findings provide evidence for the hypothesis that the functional interplay of both promoters contributes to the temporal pattern of BFV transcription and suggest that a post-transcriptional regulation exist in BFV replication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. J. Attal, M.C. Theron, F. Taboit, M. Cajero-Juarez, G. Kann, P. Bolifraud, L.M. Houdebine, The RU5 (‘R’) region from human leukaemia viruses (HTLV-1) contains an internal ribosome entry site (IRES)-like sequence. FEBS Lett. 392, 220–224 (1996)

    Article  CAS  Google Scholar 

  2. A. Bashirullah, R.L. Cooperstock, H.D. Lipshitz, RNA localization in development. Annu. Rev. Biochem. 67, 335–394 (1998)

    Article  CAS  Google Scholar 

  3. D. Beckett, O.C. Uhlenbeck, Ribonucleoprotein complexes of R17 coat protein and a translational operator analog. J. Mol. Biol. 204, 927–938 (1988)

    Article  CAS  Google Scholar 

  4. C.A. Beelman, R. Parker, Degradation of mRNA in eukaryotes. Cell 81, 179–183 (1995)

    Article  CAS  Google Scholar 

  5. C. Berlioz, C. Torrent, J.L. Darlix, An internal ribosomal entry signal in the rat VL30 region of the Harvey murine sarcoma virus leader and its use in dicistronic retroviral vectors. J. Virol. 69, 6400–6407 (1995)

    CAS  PubMed  PubMed Central  Google Scholar 

  6. J. Bodem, M. Lochelt, P. Yang, R.M. Flugel, Regulation of gene expression by human foamy virus and potentials of foamy viral vectors. Stem Cells 15(Suppl 1), 141–147 (1997)

    Article  CAS  Google Scholar 

  7. A. Brasey, M. Lopez-Lastra, T. Ohlmann, N. Beerens, B. Berkhout, J.L. Darlix, N. Sonenberg, The leader of human immunodeficiency virus type 1 genomic RNA harbors an internal ribosome entry segment that is active during the G2/M phase of the cell cycle. J. Virol. 77, 3939–3949 (2003)

    Article  CAS  Google Scholar 

  8. M. Bray, S. Prasad, J.W. Dubay, E. Hunter, K.T. Jeang, D. Rekosh, M.L. Hammarskjold, A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc. Natl. Acad. Sci. USA 91, 1256–1260 (1994)

    Article  CAS  Google Scholar 

  9. E.A. Brown, A.J. Zajac, S.M. Lemon, In vitro characterization of an internal ribosomal entry site (IRES) present within the 5′ nontranslated region of hepatitis A virus RNA: comparison with the IRES of encephalomyocarditis virus. J. Virol. 68, 1066–1074 (1994)

    CAS  PubMed  PubMed Central  Google Scholar 

  10. B.R. Cullen, Mechanism of action of regulatory proteins encoded by complex retroviruses. Microbiol. Rev. 56, 375–394 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  11. B.R. Cullen, Nuclear RNA export pathways. Mol. Cell. Biol. 20, 4181–4187 (2000)

    Article  CAS  Google Scholar 

  12. D. Curtis, R. Lehmann, P.D. Zamore, Translational regulation in development. Cell 81, 171–178 (1995)

    Article  CAS  Google Scholar 

  13. F. Delebecque, R. Suspene, S. Calattini, N. Casartelli, A. Saib, A. Froment, S. Wain-Hobson, A. Gessain, J.P. Vartanian, O. Schwartz, Restriction of foamy viruses by APOBEC cytidine deaminases. J. Virol. 80, 605–614 (2006)

    Article  CAS  Google Scholar 

  14. Y. Durocher, S. Perret, A. Kamen, High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells. Nucleic Acids Res. 30, E9 (2002)

    Article  Google Scholar 

  15. R.K. Ernst, M. Bray, D. Rekosh, M.L. Hammarskjold, A structured retroviral RNA element that mediates nucleocytoplasmic export of intron-containing RNA. Mol. Cell. Biol. 17, 135–144 (1997)

    Article  CAS  Google Scholar 

  16. B.K. Felber, M. Hadzopoulou-Cladaras, C. Cladaras, T. Copeland, G.N. Pavlakis, rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc. Natl. Acad. Sci. USA 86, 1495–1499 (1989)

    Article  CAS  Google Scholar 

  17. D. Fusco, N. Accornero, B. Lavoie, S.M. Shenoy, J.M. Blanchard, R.H. Singer, E. Bertrand, Single mRNA molecules demonstrate probabilistic movement in living mammalian cells. Curr. Biol. 13, 161–167 (2003)

    Article  CAS  Google Scholar 

  18. C.L. Hill, P.D. Bieniasz, M.O. McClure, Properties of human foamy virus relevant to its development as a vector for gene therapy. J. Gen. Virol. 80(Pt 8), 2003–2009 (1999)

    Article  CAS  Google Scholar 

  19. R.P. Jansen, mRNA localization: message on the move. Nat. Rev. Mol. Cell Biol. 2, 247–256 (2001)

    Article  CAS  Google Scholar 

  20. J. Tan, K. Wu, R. Chang, Q. Chen, Y. Geng, W. Qiao, Subcellular localization analysis of bovine foamy virus Borf1 protein. Virol. Sin. 23, 37–42 (2008)

    Article  CAS  Google Scholar 

  21. Y. Kang, W.S. Blair, B.R. Cullen, Identification and functional characterization of a high-affinity Bel-1 DNA binding site located in the human foamy virus internal promoter. J. Virol. 72, 504–511 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. C.H. Lecellier, M. Neves, M.L. Giron, J. Tobaly-Tapiero, A. Saib, Further characterization of equine foamy virus reveals unusual features among the foamy viruses. J. Virol. 76, 7220–7227 (2002)

    Article  CAS  Google Scholar 

  23. M. Linial, Why aren’t foamy viruses pathogenic? Trends Microbiol. 8, 284–289 (2000)

    Article  CAS  Google Scholar 

  24. M.L. Linial, Foamy viruses are unconventional retroviruses. J. Virol. 73, 1747–1755 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  25. M. Lochelt, Foamy virus transactivation and gene expression. Curr. Top. Microbiol. Immunol. 277, 27–61 (2003)

    CAS  PubMed  Google Scholar 

  26. M. Lochelt, R.M. Flugel, The molecular biology of human and primate spuma retroviruses, in The Retroviridae, vol. 4, ed. by J.A. Levy (Plenum Press, New York, 1995), pp. 239–292

    Chapter  Google Scholar 

  27. M. Lochelt, M. Aboud, R.M. Flugel, Increase in the basal transcriptional activity of the human foamy virus internal promoter by the homologous long terminal repeat promoter in cis. Nucleic Acids Res. 21, 4226–4230 (1993)

    Article  CAS  Google Scholar 

  28. M. Lochelt, R.M. Flugel, M. Aboud, The human foamy virus internal promoter directs the expression of the functional Bel 1 transactivator and Bet protein early after infection. J. Virol. 68, 638–645 (1994)

    CAS  PubMed  PubMed Central  Google Scholar 

  29. M. Lopez-Lastra, C. Gabus, J.L. Darlix, Characterization of an internal ribosomal entry segment within the 5′ leader of avian reticuloendotheliosis virus type A RNA and development of novel MLV-REV-based retroviral vectors. Hum. Gene Ther. 8, 1855–1865 (1997)

    Article  CAS  Google Scholar 

  30. M.H. Malim, J. Hauber, S.Y. Le, J.V. Maizel, B.R. Cullen, The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 338, 254–257 (1989)

    Article  CAS  Google Scholar 

  31. C.D. Meiering, C. Rubio, C. May, M.L. Linial, Cell-type-specific regulation of the two foamy virus promoters. J. Virol. 75, 6547–6557 (2001)

    Article  CAS  Google Scholar 

  32. F. Mignone, C. Gissi, S. Liuni, G. Pesole, Untranslated regions of mRNAs. Genome Biol. 3, REVIEWS0004 (2002)

    Article  Google Scholar 

  33. P. Mitchell, D. Tollervey, mRNA turnover. Curr. Opin. Cell Biol. 13, 320–325 (2001)

    Article  CAS  Google Scholar 

  34. U. Nestler, M. Heinkelein, M. Lucke, J. Meixensberger, W. Scheurlen, A. Kretschmer, A. Rethwilm, Foamy virus vectors for suicide gene therapy. Gene Ther. 4, 1270–1277 (1997)

    Article  CAS  Google Scholar 

  35. R.E. Paca, R.A. Ogert, C.S. Hibbert, E. Izaurralde, K.L. Beemon, Rous sarcoma virus DR posttranscriptional elements use a novel RNA export pathway. J. Virol. 74, 9507–9514 (2000)

    Article  CAS  Google Scholar 

  36. A.E. Pasquinelli, R.K. Ernst, E. Lund, C. Grimm, M.L. Zapp, D. Rekosh, M.L. Hammarskjold, J.E. Dahlberg, The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) accesses a cellular mRNA export pathway. EMBO J. 16, 7500–7510 (1997)

    Article  CAS  Google Scholar 

  37. G. Pesole, S. Liuni, G. Grillo, F. Licciulli, F. Mignone, C. Gissi, C. Saccone, UTRdb and UTRsite: specialized databases of sequences and functional elements of 5′ and 3′ untranslated regions of eukaryotic mRNAs. Update 2002. Nucleic Acids Res. 30, 335–340 (2002)

    Article  CAS  Google Scholar 

  38. R.W. Renshaw, J.W. Casey, Transcriptional mapping of the 3′ end of the bovine syncytial virus genome. J. Virol. 68, 1021–1028 (1994)

    CAS  PubMed  PubMed Central  Google Scholar 

  39. R.C. Rijnbrand, S.M. Lemon, Internal ribosome entry site-mediated translation in hepatitis C virus replication. Curr. Top. Microbiol. Immunol. 242, 85–116 (2000)

    CAS  PubMed  Google Scholar 

  40. M.S. Rook, M. Lu, K.S. Kosik, CaMKIIalpha 3′ untranslated region-directed mRNA translocation in living neurons: visualization by GFP linkage. J. Neurosci. 20, 6385–6393 (2000)

    Article  CAS  Google Scholar 

  41. J. Ross, mRNA stability in mammalian cells. Microbiol. Rev. 59, 423–450 (1995)

    CAS  PubMed  PubMed Central  Google Scholar 

  42. D.W. Russell, A.D. Miller, Foamy virus vectors. J. Virol. 70, 217–222 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  43. R.A. Russell, H.L. Wiegand, M.D. Moore, A. Schafer, M.O. McClure, B.R. Cullen, Foamy virus Bet proteins function as novel inhibitors of the APOBEC3 family of innate antiretroviral defense factors. J. Virol. 79, 8724–8731 (2005)

    Article  CAS  Google Scholar 

  44. C. Saavedra, B. Felber, E. Izaurralde, The simian retrovirus-1 constitutive transport element, unlike the HIV-1 RRE, uses factors required for cellular mRNA export. Curr. Biol. 7, 619–628 (1997)

    Article  CAS  Google Scholar 

  45. J. Sodroski, W.C. Goh, C. Rosen, A. Dayton, E. Terwilliger, W. Haseltine, A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature 321, 412–417 (1986)

    Article  CAS  Google Scholar 

  46. B. Taddeo, A. Esclatine, W. Zhang, B. Roizman, The stress-inducible immediate-early responsive gene IEX-1 is activated in cells infected with herpes simplex virus 1, but several viral mechanisms, including 3′ degradation of its RNA, preclude expression of the gene. J. Virol. 77, 6178–6187 (2003)

    Article  CAS  Google Scholar 

  47. J. Tan, W. Qiao, J. Wang, F. Xu, Y. Li, J. Zhou, Q. Chen, Y. Geng, IFP35 is involved in the antiviral function of interferon by association with the viral tas transactivator of bovine foamy virus. J. Virol. 82, 4275–4283 (2008)

    Article  CAS  Google Scholar 

  48. K. Tsukiyama-Kohara, N. Iizuka, M. Kohara, A. Nomoto, Internal ribosome entry site within hepatitis C virus RNA. J. Virol. 66, 1476–1483 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  49. S. Vagner, A. Waysbort, M. Marenda, M.C. Gensac, F. Amalric, A.C. Prats, Alternative translation initiation of the Moloney murine leukemia virus mRNA controlled by internal ribosome entry involving the p57/PTB splicing factor. J. Biol. Chem. 270, 20376–20383 (1995)

    Article  CAS  Google Scholar 

  50. S. Vagner, B. Galy, S. Pyronnet, Irresistible IRES. Attracting the translation machinery to internal ribosome entry sites. EMBO Rep. 2, 893–898 (2001)

    Article  CAS  Google Scholar 

  51. K. Valegard, J.B. Murray, N.J. Stonehouse, S. van den Worm, P.G. Stockley, L. Liljas, The three-dimensional structures of two complexes between recombinant MS2 capsids and RNA operator fragments reveal sequence-specific protein–RNA interactions. J. Mol. Biol. 270, 724–738 (1997)

    Article  CAS  Google Scholar 

  52. A.W. van der Velden, A.A. Thomas, The role of the 5′ untranslated region of an mRNA in translation regulation during development. Int. J. Biochem. Cell Biol. 31, 87–106 (1999)

    Article  Google Scholar 

  53. H. Wodrich, J. Bohne, E. Gumz, R. Welker, H.G. Krausslich, A new RNA element located in the coding region of a murine endogenous retrovirus can functionally replace the Rev/Rev-responsive element system in human immunodeficiency virus type 1 Gag expression. J. Virol. 75, 10670–10682 (2001)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Professor Chen Liang (Micgill University, Canada) for providing plasmids for this study. This work was supported by the National Basic Research Program of China (2005CB522903) and the National Natural Science Foundation of China (30570072).

Author information

Authors and Affiliations

  1. Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin, 300071, China

    Wei Wang, Juan Tan, Jian Wang, Qimin Chen, Yunqi Geng & Wentao Qiao

  2. Pediatric Research Institute, Tianjin Children’s Hospital, Tianjin, 300074, China

    Wei Wang

  3. State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, Nankai University, Tianjin, 300071, China

    Juan Tan

Authors
  1. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qimin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yunqi Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wentao Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wentao Qiao.

Additional information

Wei Wang and Juan Tan contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, W., Tan, J., Wang, J. et al. Analysis of bovine foamy virus btas mRNA transcripts during persistent infection. Virus Genes 40, 84–93 (2010). https://doi.org/10.1007/s11262-009-0422-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11262-009-0422-6

Keywords

Search

Navigation