Abstract
RNA-RNA recombination between different strains of the murine coronavirus mouse hepatitis virus (MHV) occurs at a very high frequency in tissue culture. To demonstrate that RNA recombination may play a role in the evolution and pathogenesis of coronaviruses, we sought to determine whether MHV recombination could occur during replication in the animal host of the virus. By using two selectable markers, i.e., temperature sensitivity and monoclonal antibody neutralization, we isolated several recombinant viruses from the brains of mice infected with two different strains of MHV. The recombination frequency was very high, and recombination occurred at multiple sites on the viral RNA genome. This finding suggests that RNA-RNA recombination may play a significant role in natural evolution and neuropathogenesis of coronaviruses.
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- Baric R. S., Shieh C. K., Stohlman S. A., Lai M. M. Analysis of intracellular small RNAs of mouse hepatitis virus: evidence for discontinuous transcription. Virology. 1987 Feb;156(2):342–354. doi: 10.1016/0042-6822(87)90414-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baric R. S., Stohlman S. A., Lai M. M. Characterization of replicative intermediate RNA of mouse hepatitis virus: presence of leader RNA sequences on nascent chains. J Virol. 1983 Dec;48(3):633–640. doi: 10.1128/jvi.48.3.633-640.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bujarski J. J., Kaesberg P. Genetic recombination between RNA components of a multipartite plant virus. 1986 May 29-Jun 4Nature. 321(6069):528–531. doi: 10.1038/321528a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burks J. S., DeVald B. L., Jankovsky L. D., Gerdes J. C. Two coronaviruses isolated from central nervous system tissue of two multiple sclerosis patients. Science. 1980 Aug 22;209(4459):933–934. doi: 10.1126/science.7403860. [DOI] [PubMed] [Google Scholar]
- Fleming J. O., Trousdale M. D., el-Zaatari F. A., Stohlman S. A., Weiner L. P. Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies. J Virol. 1986 Jun;58(3):869–875. doi: 10.1128/jvi.58.3.869-875.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirano N., Fujiwara K., Hino S., Matumoto M. Replication and plaque formation of mouse hepatitis virus (MHV-2) in mouse cell line DBT culture. Arch Gesamte Virusforsch. 1974;44(3):298–302. doi: 10.1007/BF01240618. [DOI] [PubMed] [Google Scholar]
- Holland J., Spindler K., Horodyski F., Grabau E., Nichol S., VandePol S. Rapid evolution of RNA genomes. Science. 1982 Mar 26;215(4540):1577–1585. doi: 10.1126/science.7041255. [DOI] [PubMed] [Google Scholar]
- Javier R. T., Sedarati F., Stevens J. G. Two avirulent herpes simplex viruses generate lethal recombinants in vivo. Science. 1986 Nov 7;234(4777):746–748. doi: 10.1126/science.3022376. [DOI] [PubMed] [Google Scholar]
- Keck J. G., Stohlman S. A., Soe L. H., Makino S., Lai M. M. Multiple recombination sites at the 5'-end of murine coronavirus RNA. Virology. 1987 Feb;156(2):331–341. doi: 10.1016/0042-6822(87)90413-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- King A. M., McCahon D., Slade W. R., Newman J. W. Recombination in RNA. Cell. 1982 Jul;29(3):921–928. doi: 10.1016/0092-8674(82)90454-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lai M. M., Baric R. S., Brayton P. R., Stohlman S. A. Characterization of leader RNA sequences on the virion and mRNAs of mouse hepatitis virus, a cytoplasmic RNA virus. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3626–3630. doi: 10.1073/pnas.81.12.3626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lai M. M., Baric R. S., Makino S., Keck J. G., Egbert J., Leibowitz J. L., Stohlman S. A. Recombination between nonsegmented RNA genomes of murine coronaviruses. J Virol. 1985 Nov;56(2):449–456. doi: 10.1128/jvi.56.2.449-456.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lai M. M., Brayton P. R., Armen R. C., Patton C. D., Pugh C., Stohlman S. A. Mouse hepatitis virus A59: mRNA structure and genetic localization of the sequence divergence from hepatotropic strain MHV-3. J Virol. 1981 Sep;39(3):823–834. doi: 10.1128/jvi.39.3.823-834.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lai M. M., Patton C. D., Baric R. S., Stohlman S. A. Presence of leader sequences in the mRNA of mouse hepatitis virus. J Virol. 1983 Jun;46(3):1027–1033. doi: 10.1128/jvi.46.3.1027-1033.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lai M. M., Stohlman S. A. RNA of mouse hepatitis virus. J Virol. 1978 May;26(2):236–242. doi: 10.1128/jvi.26.2.236-242.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Langridge J., Langridge P., Bergquist P. L. Extraction of nucleic acids from agarose gels. Anal Biochem. 1980 Apr;103(2):264–271. doi: 10.1016/0003-2697(80)90266-3. [DOI] [PubMed] [Google Scholar]
- Larson H. E., Reed S. E., Tyrrell D. A. Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J Med Virol. 1980;5(3):221–229. doi: 10.1002/jmv.1890050306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Makino S., Fleming J. O., Keck J. G., Stohlman S. A., Lai M. M. RNA recombination of coronaviruses: localization of neutralizing epitopes and neuropathogenic determinants on the carboxyl terminus of peplomers. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6567–6571. doi: 10.1073/pnas.84.18.6567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Makino S., Keck J. G., Stohlman S. A., Lai M. M. High-frequency RNA recombination of murine coronaviruses. J Virol. 1986 Mar;57(3):729–737. doi: 10.1128/jvi.57.3.729-737.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Makino S., Taguchi F., Hirano N., Fujiwara K. Analysis of genomic and intracellular viral RNAs of small plaque mutants of mouse hepatitis virus, JHM strain. Virology. 1984 Nov;139(1):138–151. doi: 10.1016/0042-6822(84)90335-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minor P. D., John A., Ferguson M., Icenogle J. P. Antigenic and molecular evolution of the vaccine strain of type 3 poliovirus during the period of excretion by a primary vaccinee. J Gen Virol. 1986 Apr;67(Pt 4):693–706. doi: 10.1099/0022-1317-67-4-693. [DOI] [PubMed] [Google Scholar]
- Stohlman S. A., Brayton P. R., Fleming J. O., Weiner L. P., Lai M. M. Murine coronaviruses: isolation and characterization of two plaque morphology variants of the JHM neurotropic strain. J Gen Virol. 1982 Dec;63(2):265–275. doi: 10.1099/0022-1317-63-2-265. [DOI] [PubMed] [Google Scholar]
- Wege H., Müller A., ter Meulen V. Genomic RNA of the murine coronavirus JHM. J Gen Virol. 1978 Nov;41(2):217–227. doi: 10.1099/0022-1317-41-2-217. [DOI] [PubMed] [Google Scholar]
- Weiner L. P. Pathogenesis of demyelination induced by a mouse hepatitis. Arch Neurol. 1973 May;28(5):298–303. doi: 10.1001/archneur.1973.00490230034003. [DOI] [PubMed] [Google Scholar]