Polyprotein Processing of Theiler's Murine Encephalomyelitis Virus

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1989 Dec 1

PMID 2555559

Citations 24

Authors

R P Roos

W P Kong

B L Semler

Affiliations

Soon will be listed here.

Abstract

To investigate polyprotein processing of Theiler's murine encephalomyelitis viruses, we analyzed in vitro translation reactions programmed by in vitro-derived transcripts from an infectious full-length cDNA clone of the DA strain of Theiler's virus. To help identify the proteinases that carried out the processing, we modified the DA cDNA clone transcription template by linearization with different restriction endonucleases that generate templates of different lengths or by constructing linker insertion or deletion mutations or both in putative proteinase-coding regions. Protein 3C carried out most of the cleavages of the polyprotein, as is true for the other picornaviruses that have been studied. A second proteinase also appeared active at the LP12A-2B junction. A protein of slightly faster mobility than the leader protein was seen with translation of transcripts derived from DA cDNA but not GDVII cDNA. This protein may be synthesized from an alternative initiation site in the DA leader-coding region out of phase with the polyprotein reading frame. Our findings are relevant to ongoing investigations of the abnormal virus expression seen in DA virus late demyelinating disease, since polyprotein processing is critical in regulating picornaviral gene expression.

Citing Articles

Characterization of Plaque-Sized Variants of Daniel's (DA) Strain in Theiler's Virus-Induced Epilepsy.

Bijalwan M, Young C, Tingling J, Zhou X, Rimmelin A, Leibowitz J Sci Rep. 2019; 9(1):3444.

PMID: 30837498 PMC: 6401140. DOI: 10.1038/s41598-019-38967-z.

A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L.

Drappier M, Jha B, Stone S, Elliott R, Zhang R, Vertommen D PLoS Pathog. 2018; 14(4):e1006989.

PMID: 29652922 PMC: 5927464. DOI: 10.1371/journal.ppat.1006989.

Theiler's murine encephalomyelitis virus contrasts with encephalomyocarditis and foot-and-mouth disease viruses in its functional utilization of the StopGo non-standard translation mechanism.

Loughran G, Libbey J, Uddowla S, Scallan M, Ryan M, Fujinami R J Gen Virol. 2012; 94(Pt 2):348-353.

PMID: 23100365 PMC: 3709618. DOI: 10.1099/vir.0.047571-0.

Theiler's virus L* protein is targeted to the mitochondrial outer membrane.

Sorgeloos F, Vertommen D, Rider M, Michiels T J Virol. 2011; 85(7):3690-4.

PMID: 21228226 PMC: 3067834. DOI: 10.1128/JVI.02023-10.

Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression.

Ricour C, Borghese F, Sorgeloos F, Hato S, van Kuppeveld F, Michiels T J Virol. 2009; 83(21):11223-32.

PMID: 19710133 PMC: 2772802. DOI: 10.1128/JVI.00829-09.

References

Brown B, EHRENFELD E . Translation of poliovirus RNA in vitro: changes in cleavage pattern and initiation sites by ribosomal salt wash. Virology. 1979; 97(2):396-405. DOI: 10.1016/0042-6822(79)90350-7. View

Roos R, Stein S, Ohara Y, Fu J, Semler B . Infectious cDNA clones of the DA strain of Theiler's murine encephalomyelitis virus. J Virol. 1989; 63(12):5492-6. PMC: 251223. DOI: 10.1128/JVI.63.12.5492-5496.1989. View

Lorch Y, Friedmann A, Lipton H, Kotler M . Theiler's murine encephalomyelitis virus group includes two distinct genetic subgroups that differ pathologically and biologically. J Virol. 1981; 40(2):560-7. PMC: 256659. DOI: 10.1128/JVI.40.2.560-567.1981. View

Hanecak R, Semler B, Anderson C, Wimmer E . Proteolytic processing of poliovirus polypeptides: antibodies to polypeptide P3-7c inhibit cleavage at glutamine-glycine pairs. Proc Natl Acad Sci U S A. 1982; 79(13):3973-7. PMC: 346558. DOI: 10.1073/pnas.79.13.3973. View

Campbell E, Jackson R . Processing of the encephalomyocarditis virus capsid precursor protein studied in rabbit reticulocyte lysates incubated with N-formyl-[35S]methionine-tRNAfMet. J Virol. 1983; 45(1):439-41. PMC: 256426. DOI: 10.1128/JVI.45.1.439-441.1983. View

Semler B, Hanecak R, Dorner L, Anderson C, Wimmer E . Poliovirus RNA synthesis in vitro: structural elements and antibody inhibition. Virology. 1983; 126(2):624-35. DOI: 10.1016/s0042-6822(83)80018-x. View

Dorner A, Semler B, Jackson R, Hanecak R, Duprey E, Wimmer E . In vitro translation of poliovirus RNA: utilization of internal initiation sites in reticulocyte lysate. J Virol. 1984; 50(2):507-14. PMC: 255658. DOI: 10.1128/JVI.50.2.507-514.1984. View

Nitayaphan S, Toth M, Roos R . Neutralizing monoclonal antibodies to Theiler's murine encephalomyelitis viruses. J Virol. 1985; 53(2):651-7. PMC: 254681. DOI: 10.1128/JVI.53.2.651-657.1985. View

Mosenkis J, Janovec S, Duncan R, Hershey J, Grifo J, Merrick W . Shutoff of host translation by encephalomyocarditis virus infection does not involve cleavage of the eucaryotic initiation factor 4F polypeptide that accompanies poliovirus infection. J Virol. 1985; 54(2):643-5. PMC: 254842. DOI: 10.1128/JVI.54.2.643-645.1985. View

10.

Cash E, Chamorro M, Brahic M . Theiler's virus RNA and protein synthesis in the central nervous system of demyelinating mice. Virology. 1985; 144(1):290-4. DOI: 10.1016/0042-6822(85)90327-7. View

11.

Clarke B, Sangar D, Burroughs J, Newton S, Carroll A, Rowlands D . Two initiation sites for foot-and-mouth disease virus polyprotein in vivo. J Gen Virol. 1985; 66 ( Pt 12):2615-26. DOI: 10.1099/0022-1317-66-12-2615. View

12.

Jackson R . A detailed kinetic analysis of the in vitro synthesis and processing of encephalomyocarditis virus products. Virology. 1986; 149(1):114-27. DOI: 10.1016/0042-6822(86)90092-9. View

13.

Strebel K, Beck E . A second protease of foot-and-mouth disease virus. J Virol. 1986; 58(3):893-9. PMC: 252997. DOI: 10.1128/JVI.58.3.893-899.1986. View

14.

Toyoda H, Nicklin M, Murray M, Anderson C, Dunn J, Studier F . A second virus-encoded proteinase involved in proteolytic processing of poliovirus polyprotein. Cell. 1986; 45(5):761-70. DOI: 10.1016/0092-8674(86)90790-7. View

15.

Parks G, Duke G, Palmenberg A . Encephalomyocarditis virus 3C protease: efficient cell-free expression from clones which link viral 5' noncoding sequences to the P3 region. J Virol. 1986; 60(2):376-84. PMC: 288903. DOI: 10.1128/JVI.60.2.376-384.1986. View

16.

Semler B . In vitro molecular genetics as a tool for determining the differential cleavage specificities of the poliovirus 3C proteinase. Nucleic Acids Res. 1987; 15(5):2069-88. PMC: 340618. DOI: 10.1093/nar/15.5.2069. View

17.

Pevear D, Calenoff M, Rozhon E, Lipton H . Analysis of the complete nucleotide sequence of the picornavirus Theiler's murine encephalomyelitis virus indicates that it is closely related to cardioviruses. J Virol. 1987; 61(5):1507-16. PMC: 254129. DOI: 10.1128/JVI.61.5.1507-1516.1987. View

18.

Sangar D, Newton S, Rowlands D, Clarke B . All foot and mouth disease virus serotypes initiate protein synthesis at two separate AUGs. Nucleic Acids Res. 1987; 15(8):3305-15. PMC: 340731. DOI: 10.1093/nar/15.8.3305. View

19.

Nitayaphan S, Omilianowski D, Toth M, Parks G, Rueckert R, Palmenberg A . Relationship of Theiler's murine encephalomyelitis viruses to the cardiovirus genus of picornaviruses. Intervirology. 1986; 26(3):140-8. DOI: 10.1159/000149693. View

20.

Nicklin M, Krausslich H, Toyoda H, Dunn J, Wimmer E . Poliovirus polypeptide precursors: expression in vitro and processing by exogenous 3C and 2A proteinases. Proc Natl Acad Sci U S A. 1987; 84(12):4002-6. PMC: 305009. DOI: 10.1073/pnas.84.12.4002. View