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Efficient replication, and evolution of Sindbis virus genomes with non-canonical 3′A/U-rich elements (NC3ARE) in neonatal mice

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An Erratum to this article was published on 06 January 2009

Abstract

Sindbis virus (SIN) is a mosquito-transmitted animal RNA virus. We previously reported that SIN genomes lacking a canonical 19 nt 3′CSE undergo novel repair processes in BHK cells to generate a library of stable atypical SIN genomes with non-canonical 3′A/U-rich elements (NC3AREs) adjacent to the 3′ poly(A) tail [1]. To determine the stability and evolutionary pressures on the SIN genomes with NC3AREs to regain a 3′CSE, five representative SIN isolates and a wild type SIN were tested in newborn mice. The key findings of this study are: (a) all six SIN isolates, including those that have extensive NC3AREs in the 3′NTRs, replicate well and produce high titer viremia in newborn mice; (b) 7–9 successive passages of these isolates in newborn mice produced comparable levels of viremia; (c) while all isolates produced only small-sized plaques during primary infection in animals, both small- and large-sized plaques were generated in all other passages; (d) polymerase stuttering occurs on select 3′ oligo(U) motifs to add more U residues within the NC3AREs; (e) the S3–8 isolate with an internal UAUUU motif in the 3′poly(A) tail maintains this element even after 9 passages in animals; (f) despite differences in 3′NTRs and variable tissue distribution, all SIN isolates appear to produce similar tissue pathology in infected animals. Competition experiments with wt SIN and atypical SIN isolates in BHK cells show dominance of wt SIN. As shown for BHK cells in culture, the 3′CSE of the SIN genome is not required for virus replication and genome stability in live animals. Since the NC3AREs of atypical SIN genomes are not specific to SIN replicases, alternate RNA motifs of alphavirus genome must confer specificity in template selection. These studies fulfill the need to confirm the long-term viability of atypical SIN genomes in newborn mice and offer a basis for exploring the use of atypical SIN genomes in biotechnology.

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References

  1. J. George, R. Raju, J. Virol. 74, 9776–9785 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. D.E. Griffin in D.M. Knipe, P.M. Howley (eds), Fields Virology (Lippincott, Williams and Wilkins, Philadelphia, PA, 2001), pp. 917–962

  3. J.H. Strauss, E.G. Strauss, Microbiol. Rev. 58, 491–562 (1994)

    CAS  PubMed  PubMed Central  Google Scholar 

  4. R.E. Johnston, C.J. Peters in B.N. Fields, D.M. Knipe, P.M. Howley (eds), Fields Virology (Lippincott-Raven, Philadelphia, PA, 1996), pp. 843–898

  5. R. Raju, M. Hajjou, K.R. Hill, V. Botta, S. Botta, J. Virol. 73, 2410–2419 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  6. N. Pardigon, E. Lenches, J.H. Strauss, J. Virol. 67, 5003–5011 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  7. R. Levis, B.G. Weiss, M. Tsiang, H. Huang, S. Schlesinger, Cell 44, 137–145 (1986)

    Article  CAS  PubMed  Google Scholar 

  8. R.J. Kuhn, Z. Hong, J.H. Strauss, J. Virol. 64, 1465–1476 (1990)

    CAS  PubMed  PubMed Central  Google Scholar 

  9. K.R. Hill, M. Hajjou, J.Y. Hu, R. Raju, J. Virol. 71, 2693–2704 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  10. M. Hajjou, K.R. Hill, S.V. Subramaniam, J.Y. Hu, R. Raju, J. Virol. 70, 5153–5164 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  11. M.H. Chen, T.K. Frey, J. Virol. 73, 3386–3403 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Y.Y. Kusov, R. Gosert, V. Gauss-Muller, J. Gen. Virol. 86, 1363–1368 (2005)

    Article  CAS  PubMed  Google Scholar 

  13. M.J. van Ooij, C. Polacek, D.H. Glaudemans, J. Kuijpers, F.J. van Kuppeveld, R. Andino, V.I. Agol, W.J. Melchers, Nucleic. Acids. Res. 34, 2953–2965 (2006)

    Article  PubMed  PubMed Central  Google Scholar 

  14. I. Frolov, R. Hardy, C.M. Rice, Rna. 7, 1638–1651 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. R.W. Hardy, Virology. 345, 520–531 (2006)

    Article  CAS  PubMed  Google Scholar 

  16. R.W. Hardy, C.M. Rice, J. Virol. 79, 4630–4639 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. S. Tomar, R.W. Hardy, J.L. Smith, R.J. Kuhn, J. Virol. 80, 9962–9969 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. M.A. Thal, B.R. Wasik, J. Posto, R.W. Hardy, Virology. 358, 221–232 (2007)

    Article  CAS  PubMed  Google Scholar 

  19. A.C. Verrotti, S.R. Thompson, C. Wreden, S. Strickland, M. Wickens, Proc. Natl. Acad. Sci. USA 93, 9027–9032 (1996)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. C. Barreau, L. Paillard, H.B. Osborne, Nucleic Acids Res. 33, 7138–7150 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. C.J. Decker, R. Parker, Curr. Opin. Cell Biol. 7, 386–392 (1995)

    Article  CAS  PubMed  Google Scholar 

  22. T.W. Dreher, Annu. Rev. Phytopathol. 37, 151–174 (1999)

    Article  CAS  PubMed  Google Scholar 

  23. C.Y. Chen, A.B. Shyu, Trends Biochem. Sci. 20, 465–470 (1995)

    Article  CAS  PubMed  Google Scholar 

  24. J. Zhang, A.E. Simon, Virology. 333, 301–315 (2005)

    Article  CAS  PubMed  Google Scholar 

  25. R. Gorchakov, R. Hardy, C.M. Rice, I. Frolov, J. Virol. 78, 61–75 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. I.P. Greene, E. Wang, E.R. Deardorff, R. Milleron, E. Domingo, S.C. Weaver, J. Virol. 79, 14253–14260 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. A.M. Powers, A.C. Brault, Y. Shirako, E.G. Strauss, W. Kang, J.H. Strauss, S.C. Weaver, J. Virol. 75, 10118–10131 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. R.J. Kuhn, D.E. Griffin, H. Zhang, H.G. Niesters, J.H. Strauss, J. Virol. 66, 7121–7127 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  29. A.P. Byrnes, J.E. Durbin, D.E. Griffin, J. Virol. 74, 3905–3908 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. W.B. Klimstra, K.D. Ryman, R.E. Johnston, J. Virol. 72, 7357–7366(1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  31. R. Raju, D. Kolakofsky, J. Virol. 63, 122–128 (1989)

    CAS  PubMed  PubMed Central  Google Scholar 

  32. J.S. Desgrosellier, N.A. Mundell, M.A. McDonnell, H.L. Moses, J.V. Barnett, Dev. Biol. 280, 201–210 (2005)

    Article  CAS  PubMed  Google Scholar 

  33. A.P. Byrnes, D.E. Griffin, J. Virol. 74, 644–651 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. R. Raju, S.V. Subramanian, M. Hajjou, J. Virol. 69, 7391–7401 (1995)

    Google Scholar 

  35. J.H. Ou, D.W. Trent, J.H. Strauss, J. Mol. Biol. 156, 719–730 (1982)

    Article  CAS  PubMed  Google Scholar 

  36. M. Pfeffer, R.M. Kinney, O.R. Kaaden, Virology. 240, 100–108 (1998)

    Article  CAS  PubMed  Google Scholar 

  37. A.H. Khan, K. Morita, C. Parquet Md Mdel, F. Hasebe, E.G. Mathenge, A. Igarashi, J. Gen. Virol. 83, 3075–3084 (2002)

    Article  CAS  PubMed  Google Scholar 

  38. J.N. Barr, S.P. Whelan, G.W. Wertz, J. Virol. 71, 8718–8725 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  39. D.L. Sawicki, S. Perri, J.M. Polo, S.G. Sawicki, J. Virol. 80, 360–371 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by NIH grant GM57439, and MBRS-SCORE institutional program. We acknowledge the use of Molecular Biology Core Facility at Meharry, RCMI supported institutional facilities at Meharry, Vanderbilt-Meharry Alliance resources, and Vanderbilt University core facilities including DNA Core facility. We thank Lee Limbird, Diana Marver, Joel Trupin of Meharry and Grady Dwar, Louise Trent, and Palani Nalliappan of RNA-Net for their helpful comments. We also acknowledge the idea from Amiya K. Banerjee (Cleveland) that alphavirus and other RNA replicases carry A/U-rich RNAs as prosthetic components to use them as templates, to synthesize, and add A/U-rich motifs to RNA genomes.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Division of Microbial Pathogenesis and Immune Response, Meharry Medical College, School of Medicine, 1005 D.B. Todd Blvd, Nashville, TN, 37208, USA

    Frederick D. James, Katie A. Hietala, Dganit Eldar, Tiffany E. Guess & Ramaswamy Raju

  2. Department of Pathology, Meharry Medical College, School of Medicine, Nashville, TN, 37208, USA

    Cecil Cone

  3. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37211, USA

    Nathan Mundall & Joey V. Barnett

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  1. Frederick D. James
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Correspondence to Ramaswamy Raju.

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An erratum to this article is available at https://doi.org/10.1007/s11262-008-0307-0.

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James, F.D., Hietala, K.A., Eldar, D. et al. Efficient replication, and evolution of Sindbis virus genomes with non-canonical 3′A/U-rich elements (NC3ARE) in neonatal mice. Virus Genes 35, 651–662 (2007). https://doi.org/10.1007/s11262-007-0130-z

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