Abstract
The role of the negative-stranded virus accessory C proteins is difficult to assess because they appear sometimes as nonessential and thereby of no function. On the other hand, when a function is found, as in the case of Sendai virus, it represents an enigma, in that the C proteins inhibit replication under conditions where the infection follows an exponential course. Furthermore, this inhibitory function is exerted differentially: in contrast to the replication of internal deletion defective interfering (DI) RNAs, that of copy-back DI RNAs appears to escape inhibition, under certain experimental conditions (in vivo assay). In a reexamination of the C effect by the reverse genetics approach, it was found that copy-back RNA replication is inhibited by C in vivo as well, under conditions where the ratio of C to copy-back template is increased. This effect can be reversed by an increase in P but not L protein. The "rule of six" was differentially observed in the presence or absence of C. Finally, a difference in the ability of the replicating complex to tolerate promoter modifications in RNA synthesis initiation was shown to occur in the presence or the absence of C as well. We propose that C acts by increasing the selectivity of the replicating complex for the promoter cis-acting elements governing its activity. The inhibitory effect of C becomes the price to pay for this increased selectivity.
Full Text
The Full Text of this article is available as a PDF (1.9 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cadd T., Garcin D., Tapparel C., Itoh M., Homma M., Roux L., Curran J., Kolakofsky D. The Sendai paramyxovirus accessory C proteins inhibit viral genome amplification in a promoter-specific fashion. J Virol. 1996 Aug;70(8):5067–5074. doi: 10.1128/jvi.70.8.5067-5074.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Calain P., Curran J., Kolakofsky D., Roux L. Molecular cloning of natural paramyxovirus copy-back defective interfering RNAs and their expression from DNA. Virology. 1992 Nov;191(1):62–71. doi: 10.1016/0042-6822(92)90166-m. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Curran J., Kolakofsky D. Scanning independent ribosomal initiation of the Sendai virus Y proteins in vitro and in vivo. EMBO J. 1989 Feb;8(2):521–526. doi: 10.1002/j.1460-2075.1989.tb03406.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Egelman E. H., Wu S. S., Amrein M., Portner A., Murti G. The Sendai virus nucleocapsid exists in at least four different helical states. J Virol. 1989 May;63(5):2233–2243. doi: 10.1128/jvi.63.5.2233-2243.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Einberger H., Mertz R., Hofschneider P. H., Neubert W. J. Purification, renaturation, and reconstituted protein kinase activity of the Sendai virus large (L) protein: L protein phosphorylates the NP and P proteins in vitro. J Virol. 1990 Sep;64(9):4274–4280. doi: 10.1128/jvi.64.9.4274-4280.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Fuerst T. R., Niles E. G., Studier F. W., Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. doi: 10.1073/pnas.83.21.8122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Hausmann S., Jacques J. P., Kolakofsky D. Paramyxovirus RNA editing and the requirement for hexamer genome length. RNA. 1996 Oct;2(10):1033–1045. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Jacques J. P., Hausmann S., Kolakofsky D. Paramyxovirus mRNA editing leads to G deletions as well as insertions. EMBO J. 1994 Nov 15;13(22):5496–5503. doi: 10.1002/j.1460-2075.1994.tb06884.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kast W. M., Roux L., Curren J., Blom H. J., Voordouw A. C., Meloen R. H., Kolakofsky D., Melief C. J. Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2283–2287. doi: 10.1073/pnas.88.6.2283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keene J. D., Chien I. M., Lazzarini R. A. Vesicular stomatitis virus defective interfering particle containing a muted internal leader RNA gene. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2090–2094. doi: 10.1073/pnas.78.4.2090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mottet G., Mühlemann A., Tapparel C., Hoffmann F., Roux L. A Sendai virus vector leading to the efficient expression of mutant M proteins interfering with virus particle budding. Virology. 1996 Jul 1;221(1):159–171. doi: 10.1006/viro.1996.0362. [DOI] [PubMed] [Google Scholar]
- Mottet G., Roux L. Budding efficiency of Sendai virus nucleocapsids: influence of size and ends of the RNA. Virus Res. 1989 Oct;14(2):175–187. doi: 10.1016/0168-1702(89)90037-3. [DOI] [PubMed] [Google Scholar]
- Neubert W. J., Eckerskorn C., Homann H. E. Sendai virus NP gene codes for a 524 amino acid NP protein. Virus Genes. 1991 Jan;5(1):25–32. doi: 10.1007/BF00571728. [DOI] [PubMed] [Google Scholar]
- Pelet T., Delenda C., Gubbay O., Garcin D., Kolakofsky D. Partial characterization of a Sendai virus replication promoter and the rule of six. Virology. 1996 Oct 15;224(2):405–414. doi: 10.1006/viro.1996.0547. [DOI] [PubMed] [Google Scholar]
- Peluso R. W., Richardson J. C., Talon J., Lock M. Identification of a set of proteins (C' and C) encoded by the bicistronic P gene of the Indiana serotype of vesicular stomatitis virus and analysis of their effect on transcription by the viral RNA polymerase. Virology. 1996 Apr 15;218(2):335–342. doi: 10.1006/viro.1996.0202. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Shioda T., Hidaka Y., Kanda T., Shibuta H., Nomoto A., Iwasaki K. Sequence of 3,687 nucleotides from the 3' end of Sendai virus genome RNA and the predicted amino acid sequences of viral NP, P and C proteins. Nucleic Acids Res. 1983 Nov 11;11(21):7317–7330. doi: 10.1093/nar/11.21.7317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shioda T., Iwasaki K., Shibuta H. Determination of the complete nucleotide sequence of the Sendai virus genome RNA and the predicted amino acid sequences of the F, HN and L proteins. Nucleic Acids Res. 1986 Feb 25;14(4):1545–1563. doi: 10.1093/nar/14.4.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Tapparel C., Roux L. The efficiency of Sendai virus genome replication: the importance of the RNA primary sequence independent of terminal complementarity. Virology. 1996 Nov 1;225(1):163–171. doi: 10.1006/viro.1996.0584. [DOI] [PubMed] [Google Scholar]
- 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]