Abstract
Recent studies suggest that infectious viruses and particularly persisting viral RNAs often exist as diverse populations or “quasispecies”. We have developed an approach to characterize populations of the murine Coronavirus mouse hepatitis virus (MHV) generated during persistent infection which has allowed us to begin to address the role of the viral quasispecies in MHV pathogenesis. We analyzed the population of persisting viral RNAs using reverse-transcription polymerase chain reaction amplification (RT-PCR) of the S1 “hypervariable” region of the spike gene followed by differential colony hybridization to identify spike deletion variants (SDVs) from acute and persistently infected mice. Sequence analysis revealed that mice with the most severe chronic paralysis harbored the most complex quasispecies. Mapping of the SDVs to the predicted RNA secondary structure of the spike RNA revealed that an isolated stem loop structure is frequently deleted. Overall, these results are consistent with high frequency recombination at sites of RNA
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References
Adami, C., J. Pooley, J. Glomb, E. Stecker, F. Fazal, J. O. Fleming, and S. C. Baker, 1995, Evolution of mouse hepatitis virus (MHV) during chronic infection: quasispecies nature of the persisting MHV RNA, Virology 209:337–346.
Baczko, K., J. Lampe, U. G. Liebert, U. Brinckmann, V. ter Meulen, I. Pardowitz, H. Budka, S. L. Cosby, S. Is-serte, and B. K. Rima, 1993, Clonal expansion of hypermutated measles virus in a SSPE brain, Virology 197:188–195.
Bergmann, C. C., Q. Yao, M. Lin, and S. A. Stohlman, 1996, The JHM strain of mouse hepatitis virus induces a spike protein-specific Db-restricted cytotoxic T cell response, J. Gen. Virol. 77:315–325.
Cascone, P. J., T. F. Haydar, and A. E. Simon, 1993, Sequences and structures required for recombination between virus-associated RNAs, Science 260:801–805.
Castro, R. F., and S. Perlman, 1995, CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic Coronavirus and correlation with pathogenicitiy, J. Virol. 69:8127–8131.
Lai, M. M., 1992, RNA recombination in animal and plant viruses, Microbiol. Rev. 556:61–79.
Martell, M., J. I. Esteban, J. Quer, J. Genesca, A. Weiner, R. Esteban, J. Guardia, and J. Gomez., 1992, Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution, J. Virol. 66:2547–2556.
Novella, I. S., E. Domingo, and J. J. Holland, 1995, Rapid viral quasispecies evolution - implications for vaccine and drug strategies, [Review]. Molecular Medicine Today 1:248–253.
Parker, S. E., T. M. Gallagher, and M. J. Buchmeier, 1989, Sequence analysis reveals extensive polymorphism and evidence of deletions within the E2 glycoprotein gene of several strains of murine hepatitis virus, Virology 173:664–673.
Rowe, C. L., S. C. Baker, M. J. Nathan, and J. O. Fleming, 1997a, Evolution of Mouse Hepatitis Virus: Detection and Characterization of Spike Deletion Variants During Persistent Infection, J. Virol. 71:2959–2969.
Rowe, C. L., J. O. Fleming, J.-Y. Sgro, A. C. Palmenberg and S. C. Baker, 1997b, Generation of Coronavirus spike deletion variants (SDVs) by high frequency recombination at regions of predicted RNA secondary structure, J. Virol., in press.
Taguchi, F., T. Ikeda, and H. Shida, 1992, Molecular cloning and expression of a spike protein of neurovirulent murine Coronavirus JHMV variant cl-2 [published erratum appears in J Gen Virol 1992 Oct; 73(Pt10):2767], J. Gen. Virol. 73:1065–1072.
Wang, F. I., J. O. Fleming, and M. M. Lai, 1992, Sequence analysis of the spike protein gene of murine Coronavirus variants: study of genetic sites affecting neuropathogenicity, Virology 186:742–749.
White, K. A., and T. J. Morris, 1995, RNA determinants of junction site selection in RNA virus recombinants and defective interfering RNAs. RNA 1:1029–1040.
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© 1998 Springer Science+Business Media New York
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Rowe, C.L., Baker, S.C., Nathan, M.J., Sgro, JY., Palmenberg, A.C., Fleming, J.O. (1998). Quasispecies Development by High Frequency RNA Recombination during MHV Persistence. In: Enjuanes, L., Siddell, S.G., Spaan, W. (eds) Coronaviruses and Arteriviruses. Advances in Experimental Medicine and Biology, vol 440. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5331-1_98
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DOI: https://doi.org/10.1007/978-1-4615-5331-1_98
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