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. 1996 Aug;70(8):5067–5074. doi: 10.1128/jvi.70.8.5067-5074.1996

The Sendai paramyxovirus accessory C proteins inhibit viral genome amplification in a promoter-specific fashion.

T Cadd 1, D Garcin 1, C Tapparel 1, M Itoh 1, M Homma 1, L Roux 1, J Curran 1, D Kolakofsky 1
PMCID: PMC190461  PMID: 8764014

Abstract

Many paramyxoviruses express small basic C proteins, from an alternate, overlapping open reading frame of the P gene mRNA, which were previously found to inhibit mRNA synthesis. During recent experiments in which infectious Sendai virus (SeV) was recovered from cDNA via the initial expression of the viral N, P, and L genes from plasmids, the abrogation of C protein expression from the plasmid P gene was found to be necessary for virus recovery. We have investigated the effect of C coexpression on the amplification of an internally deleted defective interfering (DI) genome directly in the transfected cell, for which, in contrast to virus recovery experiments, genome amplification is independent of mRNA synthesis carried out by the SeV polymerase. We find that C protein coexpression also strongly inhibits the amplification of this DI genome but has little or no effect on that of a copy-back DI genome (DI-H4). We have also characterized the C protein from a mutant SeV and found that (i) it had lost most of its inhibitory activity on internally deleted DI genome amplification and (ii) its coexpression no longer prevented the recovery of SeV from DNA. However, consistent with the insensitivity of copy-back DI genomes to C protein inhibition, C coexpression did not prevent the recovery of copy-back nondefective viruses from DNA. The inhibitory effects of C coexpression thus appear to be promoter specific.

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Selected References

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  1. Alkhatib G., Massie B., Briedis D. J. Expression of bicistronic measles virus P/C mRNA by using hybrid adenoviruses: levels of C protein synthesized in vivo are unaffected by the presence or absence of the upstream P initiator codon. J Virol. 1988 Nov;62(11):4059–4069. doi: 10.1128/jvi.62.11.4059-4069.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Banerjee A. K., Barik S. Gene expression of vesicular stomatitis virus genome RNA. Virology. 1992 Jun;188(2):417–428. doi: 10.1016/0042-6822(92)90495-b. [DOI] [PubMed] [Google Scholar]
  3. Bellini W. J., Englund G., Rozenblatt S., Arnheiter H., Richardson C. D. Measles virus P gene codes for two proteins. J Virol. 1985 Mar;53(3):908–919. doi: 10.1128/jvi.53.3.908-919.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Calain P., Roux L. Functional characterisation of the genomic and antigenomic promoters of Sendai virus. Virology. 1995 Sep 10;212(1):163–173. doi: 10.1006/viro.1995.1464. [DOI] [PubMed] [Google Scholar]
  5. Calain P., Roux L. The rule of six, a basic feature for efficient replication of Sendai virus defective interfering RNA. J Virol. 1993 Aug;67(8):4822–4830. doi: 10.1128/jvi.67.8.4822-4830.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chandrika R., Horikami S. M., Smallwood S., Moyer S. A. Mutations in conserved domain I of the Sendai virus L polymerase protein uncouple transcription and replication. Virology. 1995 Nov 10;213(2):352–363. doi: 10.1006/viro.1995.0008. [DOI] [PubMed] [Google Scholar]
  7. Chou J., Roizman B. The gamma 1(34.5) gene of herpes simplex virus 1 precludes neuroblastoma cells from triggering total shutoff of protein synthesis characteristic of programed cell death in neuronal cells. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3266–3270. doi: 10.1073/pnas.89.8.3266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clem R. J., Fechheimer M., Miller L. K. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991 Nov 29;254(5036):1388–1390. doi: 10.1126/science.1962198. [DOI] [PubMed] [Google Scholar]
  9. Collins P. L., Hill M. G., Camargo E., Grosfeld H., Chanock R. M., Murphy B. R. Production of infectious human respiratory syncytial virus from cloned cDNA confirms an essential role for the transcription elongation factor from the 5' proximal open reading frame of the M2 mRNA in gene expression and provides a capability for vaccine development. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11563–11567. doi: 10.1073/pnas.92.25.11563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Collins P. L., Hill M. G., Cristina J., Grosfeld H. Transcription elongation factor of respiratory syncytial virus, a nonsegmented negative-strand RNA virus. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):81–85. doi: 10.1073/pnas.93.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Curran J., Boeck R., Kolakofsky D. The Sendai virus P gene expresses both an essential protein and an inhibitor of RNA synthesis by shuffling modules via mRNA editing. EMBO J. 1991 Oct;10(10):3079–3085. doi: 10.1002/j.1460-2075.1991.tb07860.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Curran J., Kolakofsky D. Sendai virus P gene produces multiple proteins from overlapping open reading frames. Enzyme. 1990;44(1-4):244–249. doi: 10.1159/000468762. [DOI] [PubMed] [Google Scholar]
  13. Curran J., Marq J. B., Kolakofsky D. The Sendai virus nonstructural C proteins specifically inhibit viral mRNA synthesis. Virology. 1992 Aug;189(2):647–656. doi: 10.1016/0042-6822(92)90588-g. [DOI] [PubMed] [Google Scholar]
  14. Curran J., Pelet T., Kolakofsky D. An acidic activation-like domain of the Sendai virus P protein is required for RNA synthesis and encapsidation. Virology. 1994 Aug 1;202(2):875–884. doi: 10.1006/viro.1994.1409. [DOI] [PubMed] [Google Scholar]
  15. Engelhorn M., Stricker R., Roux L. Molecular cloning and characterization of a Sendai virus internal deletion defective RNA. J Gen Virol. 1993 Jan;74(Pt 1):137–141. doi: 10.1099/0022-1317-74-1-137. [DOI] [PubMed] [Google Scholar]
  16. Galinski M. S., Troy R. M., Banerjee A. K. RNA editing in the phosphoprotein gene of the human parainfluenza virus type 3. Virology. 1992 Feb;186(2):543–550. doi: 10.1016/0042-6822(92)90020-P. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Garcin D., De Melo M., Roux L., Kolakofsky D., Curran J. Presence of a truncated form of the Sendai virus P protein in a long-term persistent infection: implications for the maintenance of the persistent state. Virology. 1994 May 15;201(1):19–25. doi: 10.1006/viro.1994.1261. [DOI] [PubMed] [Google Scholar]
  18. Garcin D., Kolakofsky D. A novel mechanism for the initiation of Tacaribe arenavirus genome replication. J Virol. 1990 Dec;64(12):6196–6203. doi: 10.1128/jvi.64.12.6196-6203.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Garcin D., Pelet T., Calain P., Roux L., Curran J., Kolakofsky D. A highly recombinogenic system for the recovery of infectious Sendai paramyxovirus from cDNA: generation of a novel copy-back nondefective interfering virus. EMBO J. 1995 Dec 15;14(24):6087–6094. doi: 10.1002/j.1460-2075.1995.tb00299.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Giorgi C., Blumberg B. M., Kolakofsky D. Sendai virus contains overlapping genes expressed from a single mRNA. Cell. 1983 Dec;35(3 Pt 2):829–836. doi: 10.1016/0092-8674(83)90115-0. [DOI] [PubMed] [Google Scholar]
  21. Gregory C. D., Dive C., Henderson S., Smith C. A., Williams G. T., Gordon J., Rickinson A. B. Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis. Nature. 1991 Feb 14;349(6310):612–614. doi: 10.1038/349612a0. [DOI] [PubMed] [Google Scholar]
  22. Ho S. N., Hunt H. D., Horton R. M., Pullen J. K., Pease L. R. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. doi: 10.1016/0378-1119(89)90358-2. [DOI] [PubMed] [Google Scholar]
  23. Horikami S. M., Curran J., Kolakofsky D., Moyer S. A. Complexes of Sendai virus NP-P and P-L proteins are required for defective interfering particle genome replication in vitro. J Virol. 1992 Aug;66(8):4901–4908. doi: 10.1128/jvi.66.8.4901-4908.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kestler H. W., 3rd, Ringler D. J., Mori K., Panicali D. L., Sehgal P. K., Daniel M. D., Desrosiers R. C. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 1991 May 17;65(4):651–662. doi: 10.1016/0092-8674(91)90097-i. [DOI] [PubMed] [Google Scholar]
  25. Kretzschmar E., Peluso R., Schnell M. J., Whitt M. A., Rose J. K. Normal replication of vesicular stomatitis virus without C proteins. Virology. 1996 Feb 15;216(2):309–316. doi: 10.1006/viro.1996.0066. [DOI] [PubMed] [Google Scholar]
  26. Lazinski D. W., Taylor J. M. Regulation of the hepatitis delta virus ribozymes: to cleave or not to cleave? RNA. 1995 May;1(3):225–233. [PMC free article] [PubMed] [Google Scholar]
  27. Leppert M., Kort L., Kolakofsky D. Further characterization of Sendai virus DI-RNAs: a model for their generation. Cell. 1977 Oct;12(2):539–552. doi: 10.1016/0092-8674(77)90130-1. [DOI] [PubMed] [Google Scholar]
  28. Matsuoka Y., Curran J., Pelet T., Kolakofsky D., Ray R., Compans R. W. The P gene of human parainfluenza virus type 1 encodes P and C proteins but not a cysteine-rich V protein. J Virol. 1991 Jun;65(6):3406–3410. doi: 10.1128/jvi.65.6.3406-3410.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pelet T., Curran J., Kolakofsky D. The P gene of bovine parainfluenza virus 3 expresses all three reading frames from a single mRNA editing site. EMBO J. 1991 Feb;10(2):443–448. doi: 10.1002/j.1460-2075.1991.tb07966.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Portner A., Gupta K. C., Seyer J. M., Beachey E. H., Kingsbury D. W. Localization and characterization of Sendai virus nonstructural C and C' proteins by antibodies against synthetic peptides. Virus Res. 1986 Nov;6(2):109–121. doi: 10.1016/0168-1702(86)90043-2. [DOI] [PubMed] [Google Scholar]
  31. Radecke F., Billeter M. A. The nonstructural C protein is not essential for multiplication of Edmonston B strain measles virus in cultured cells. Virology. 1996 Mar 1;217(1):418–421. doi: 10.1006/viro.1996.0134. [DOI] [PubMed] [Google Scholar]
  32. Rao L., Debbas M., Sabbatini P., Hockenbery D., Korsmeyer S., White E. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7742–7746. doi: 10.1073/pnas.89.16.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rochat S., Komada H., Kolakofsky D. Loss of V protein expression in human parainfluenza virus type 1 is not a recent event. Virus Res. 1992 Jul;24(2):137–144. doi: 10.1016/0168-1702(92)90002-q. [DOI] [PubMed] [Google Scholar]
  34. Spiropoulou C. F., Nichol S. T. A small highly basic protein is encoded in overlapping frame within the P gene of vesicular stomatitis virus. J Virol. 1993 Jun;67(6):3103–3110. doi: 10.1128/jvi.67.6.3103-3110.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Trono D. HIV accessory proteins: leading roles for the supporting cast. Cell. 1995 Jul 28;82(2):189–192. doi: 10.1016/0092-8674(95)90306-2. [DOI] [PubMed] [Google Scholar]
  36. Vidal S., Curran J., Kolakofsky D. Editing of the Sendai virus P/C mRNA by G insertion occurs during mRNA synthesis via a virus-encoded activity. J Virol. 1990 Jan;64(1):239–246. doi: 10.1128/jvi.64.1.239-246.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wang X. L., Itoh M., Hotta H., Homma M. A protease activation mutant, MVCES1, as a safe and potent live vaccine derived from currently prevailing Sendai virus. J Virol. 1994 May;68(5):3369–3373. doi: 10.1128/jvi.68.5.3369-3373.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yamada H., Hayata S., Omata-Yamada T., Taira H., Mizumoto K., Iwasaki K. Association of the Sendai virus C protein with nucleocapsids. Arch Virol. 1990;113(3-4):245–253. doi: 10.1007/BF01316677. [DOI] [PubMed] [Google Scholar]

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