The paramyxovirus, Sendai virus, V protein encodes a luxury function required for viral pathogenesis (original) (raw)

Abstract

The Sendai virus (SeV) V protein is characterized by the unique cysteine-rich domain in its carboxy-terminal half which is fused to the amino-terminal half of the P protein, but its function has remained enigmatic. The V protein-directing mRNA is generated by a remarkable process known as mRNA editing involving the pseudotemplated addition of a single G residue at a specific septinucleotide locus in the P gene, whereas the unedited exact copy encodes the P protein. Here, we introduced two nucleotide changes in the septinucleotide motif (UUUUCCC to UUCUUCC) in a full-length SeV cDNA and were able to recover a virus from the cDNA, which was devoid of mRNA editing and hence unable to synthesize the V protein. Compared with the parental wild-type virus with regard to gene expression, replication and cytopathogenicity in various cell lines in vitro, the V(-) virus was found to be either potentiated or comparable but never attenuated. The V(-) virus, however, showed markedly attenuated in vivo replication capacity in and pathogenicity for mice. Thus, though categorized as a nonessential gene product, SeV V protein encodes a luxury function required for in vivo pathogenicity.

Full Text

The Full Text of this article is available as a PDF (537.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Curran J., Kolakofsky D. Ribosomal initiation from an ACG codon in the Sendai virus P/C mRNA. EMBO J. 1988 Jan;7(1):245–251. doi: 10.1002/j.1460-2075.1988.tb02806.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Curran J., de Melo M., Moyer S., Kolakofsky D. Characterization of the Sendai virus V protein with an anti-peptide antiserum. Virology. 1991 Sep;184(1):108–116. doi: 10.1016/0042-6822(91)90827-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Hamaguchi M., Yoshida T., Nishikawa K., Naruse H., Nagai Y. Transcriptive complex of Newcastle disease virus. I. Both L and P proteins are required to constitute an active complex. Virology. 1983 Jul 15;128(1):105–117. doi: 10.1016/0042-6822(83)90322-7. [DOI] [PubMed] [Google Scholar]
  7. Harty R. N., Palese P. Measles virus phosphoprotein (P) requires the NH2- and COOH-terminal domains for interactions with the nucleoprotein (N) but only the COOH terminus for interactions with itself. J Gen Virol. 1995 Nov;76(Pt 11):2863–2867. doi: 10.1099/0022-1317-76-11-2863. [DOI] [PubMed] [Google Scholar]
  8. Ito Y., Hosaka Y. Component(s) of Sendai virus that can induce interferon in mouse spleen cells. Infect Immun. 1983 Mar;39(3):1019–1023. doi: 10.1128/iai.39.3.1019-1023.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ito Y., Nishiyama Y., Shimokata K., Takeyama H., Kunii A. Active component of HVJ (sendai virus) for interferon on induction in mice. Nature. 1978 Aug 24;274(5673):801–802. doi: 10.1038/274801a0. [DOI] [PubMed] [Google Scholar]
  10. Kato A., Fujino M., Nakamura T., Ishihama A., Otaki Y. Gene organization of chicken anemia virus. Virology. 1995 Jun 1;209(2):480–488. doi: 10.1006/viro.1995.1280. [DOI] [PubMed] [Google Scholar]
  11. Kato A., Sakai Y., Shioda T., Kondo T., Nakanishi M., Nagai Y. Initiation of Sendai virus multiplication from transfected cDNA or RNA with negative or positive sense. Genes Cells. 1996 Jun;1(6):569–579. doi: 10.1046/j.1365-2443.1996.d01-261.x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Kiyotani K., Takao S., Sakaguchi T., Yoshida T. Immediate protection of mice from lethal wild-type Sendai virus (HVJ) infections by a temperature-sensitive mutant, HVJpi, possessing homologous interfering capacity. Virology. 1990 Jul;177(1):65–74. doi: 10.1016/0042-6822(90)90460-9. [DOI] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Liston P., Briedis D. J. Measles virus V protein binds zinc. Virology. 1994 Jan;198(1):399–404. doi: 10.1006/viro.1994.1050. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Moyer S. A., Baker S. C., Lessard J. L. Tubulin: a factor necessary for the synthesis of both Sendai virus and vesicular stomatitis virus RNAs. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5405–5409. doi: 10.1073/pnas.83.15.5405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Park K. H., Krystal M. In vivo model for pseudo-templated transcription in Sendai virus. J Virol. 1992 Dec;66(12):7033–7039. doi: 10.1128/jvi.66.12.7033-7039.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Paterson R. G., Lamb R. A. RNA editing by G-nucleotide insertion in mumps virus P-gene mRNA transcripts. J Virol. 1990 Sep;64(9):4137–4145. doi: 10.1128/jvi.64.9.4137-4145.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Paterson R. G., Leser G. P., Shaughnessy M. A., Lamb R. A. The paramyxovirus SV5 V protein binds two atoms of zinc and is a structural component of virions. Virology. 1995 Apr 1;208(1):121–131. doi: 10.1006/viro.1995.1135. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Power U. F., Ryan K. W., Portner A. The P genes of human parainfluenza virus type 1 clinical isolates are polycistronic and microheterogeneous. Virology. 1992 Jul;189(1):340–343. doi: 10.1016/0042-6822(92)90712-x. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Smallwood S., Ryan K. W., Moyer S. A. Deletion analysis defines a carboxyl-proximal region of Sendai virus P protein that binds to the polymerase L protein. Virology. 1994 Jul;202(1):154–163. doi: 10.1006/viro.1994.1331. [DOI] [PubMed] [Google Scholar]
  25. Steward M., Samson A. C., Errington W., Emmerson P. T. The Newcastle disease virus V protein binds zinc. Arch Virol. 1995;140(7):1321–1328. doi: 10.1007/BF01322759. [DOI] [PubMed] [Google Scholar]
  26. Tao T., Ryan K. W. Host range restriction of parainfluenza virus growth occurs at the level of virus genome replication. Virology. 1996 Jun 1;220(1):69–77. doi: 10.1006/viro.1996.0287. [DOI] [PubMed] [Google Scholar]
  27. Thomas S. M., Lamb R. A., Paterson R. G. Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5. Cell. 1988 Sep 9;54(6):891–902. doi: 10.1016/S0092-8674(88)91285-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vidal S., Curran J., Kolakofsky D. A stuttering model for paramyxovirus P mRNA editing. EMBO J. 1990 Jun;9(6):2017–2022. doi: 10.1002/j.1460-2075.1990.tb08330.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Wardrop E. A., Briedis D. J. Characterization of V protein in measles virus-infected cells. J Virol. 1991 Jul;65(7):3421–3428. doi: 10.1128/jvi.65.7.3421-3428.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]