1887

Abstract

Hepatitis C virus (HCV) is an important human pathogen that affects 170 million people worldwide. The HCV genome is an RNA molecule that is approximately 9·6 kb in length and encodes a polyprotein that is cleaved proteolytically to generate at least 10 mature viral proteins. Recently, a new HCV protein named F has been described, which is synthesized as a result of a ribosomal frameshift. Little is known about the biological properties of this protein, but the possibility that the F protein may participate in HCV morphology or replication has been raised. In this work, the presence of functional constraints in the F protein was investigated. It was found that the rate of amino acid substitutions along the F protein was significantly higher than the rate of synonymous substitutions, and comparisons involving genes that represented independent phylogenetic lineages yielded very different divergence/conservation patterns. The distribution of stop codons in the F protein across all HCV genotypes was also investigated; genotypes 2 and 3 were found to have more stop codons than genotype 1. The results of this work suggest strongly that the pattern of divergence in the F protein is not affected by functional constraints.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80510-0
2005-01-01
2019-11-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/1/vir860115.html?itemId=/content/journal/jgv/10.1099/vir.0.80510-0&mimeType=html&fmt=ahah

References

  1. Alter, H. J. & Seeff, L. B. ( 2000; ). Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective on long-term outcome. Semin Liver Dis 20, 17–35.[CrossRef]
    [Google Scholar]
  2. Blight, K. J., Kolykhalov, A. A. & Rice, C. M. ( 2000; ). Efficient initiation of HCV RNA replication in cell culture. Science 290, 1972–1974.[CrossRef]
    [Google Scholar]
  3. Boulant, S., Becchi, M., Penin, F. & Lavergne, J.-P. ( 2003; ). Unusual multiple recoding events leading to alternative forms of hepatitis C virus core protein from genotype 1b. J Biol Chem 278, 45785–45792.[CrossRef]
    [Google Scholar]
  4. Brierley, I., Digard, P. & Inglis, S. C. ( 1989; ). Characterization of an efficient coronavirus ribosomal frameshifting signal: requirement for an RNA pseudoknot. Cell 57, 537–547.[CrossRef]
    [Google Scholar]
  5. Bukh, J., Purcell, R. H. & Miller, R. H. ( 1994; ). Sequence analysis of the core gene of 14 hepatitis C virus genotypes. Proc Natl Acad Sci U S A 91, 8239–8243.[CrossRef]
    [Google Scholar]
  6. Choi, J., Xu, Z. & Ou, J. ( 2003; ). Triple decoding of hepatitis C virus RNA by programmed translational frameshifting. Mol Cell Biol 23, 1489–1497.[CrossRef]
    [Google Scholar]
  7. Comeron, J. M. ( 1995; ). A method for estimating the numbers of synonymous and nonsynonymous substitutions per site. J Mol Evol 41, 1152–1159.
    [Google Scholar]
  8. Costa-Mattioli, M., Ferré, V., Casane, D. & 7 other authors ( 2003; ). Evidence of recombination in natural populations of hepatitis A virus. Virology 311, 51–59.[CrossRef]
    [Google Scholar]
  9. Jacks, T. & Varmus, H. E. ( 1985; ). Expression of the Rous sarcoma virus pol gene by ribosomal frameshifting. Science 230, 1237–1242.[CrossRef]
    [Google Scholar]
  10. Jukes, T. H. & Cantor, C. R. ( 1969; ). Evolution of protein molecules. In Mammalian Protein Metabolism, pp. 21–132. Edited by H. N. Munro. New York: Academic Press.
  11. Korber, B. ( 2000; ). HIV sequence signatures and similarities. In Computational and Evolutionary Analysis of HIV Molecular Sequences, pp. 55–72. Edited by A. G. Rodrigo & G. H. Learn, Jr. Dordrecht: Kluwer.
  12. Kwok, S. & Higuchi, R. ( 1989; ). Avoiding false positives with PCR. Nature 339, 237–238.[CrossRef]
    [Google Scholar]
  13. Lohmann, V., Körner, F., Koch, J.-O., Herian, U., Theilmann, L. & Bartenschlager, R. ( 1999; ). Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285, 110–113.[CrossRef]
    [Google Scholar]
  14. Marczinke, B., Bloys, A. J., Brown, T. D. K., Willcocks, M. M., Carter, M. J. & Brierley, I. ( 1994; ). The human astrovirus RNA-dependent RNA polymerase coding region is expressed by ribosomal frameshifting. J Virol 68, 5588–5595.
    [Google Scholar]
  15. Reed, K. E. & Rice, C. M. ( 2000; ). Overview of hepatitis C virus genome structure, polyprotein processing, and protein properties. Curr Top Microbiol Immunol 242, 55–84.
    [Google Scholar]
  16. Roussel, J., Pillez, A., Montpellier, C., Duverlie, G., Cahour, A., Dubuisson, J. & Wychowski, C. ( 2003; ). Characterization of the expression of the hepatitis C virus F protein. J Gen Virol 84, 1751–1759.[CrossRef]
    [Google Scholar]
  17. Simmonds, P. ( 1999; ). Viral heterogeneity of the hepatitis C virus. J Hepatol 31 (Suppl. 1), 54–60.[CrossRef]
    [Google Scholar]
  18. Thompson, J. D., Higgins, D. G. & Gibson, T. J. ( 1994; ). clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22, 4673–4680.[CrossRef]
    [Google Scholar]
  19. Xu, Z., Choi, J., Yen, T. S. B., Lu, W., Strohecker, A., Govindarajan, S., Chien, D., Selby, M. J. & Ou, J. ( 2001; ). Synthesis of a novel hepatitis C virus protein by ribosomal frameshift. EMBO J 20, 3840–3848.[CrossRef]
    [Google Scholar]
  20. Xu, Z., Choi, J., Lu, W. & Ou, J. ( 2003; ). Hepatitis C virus F protein is a short-lived protein associated with the endoplasmic reticulum. J Virol 77, 1578–1583.[CrossRef]
    [Google Scholar]
  21. Yagani, M., St Claire, M., Shapiro, M., Emerson, S. U., Purcell, R. H. & Bukh, J. ( 1998; ). Transcripts of a chimeric cDNA clone of hepatitis C virus genotype 1b are infectious in vivo. Virology 244, 161–172.[CrossRef]
    [Google Scholar]
  22. Zanotto, P. M. de A., Kallas, E. G., de Souza, R. F. & Holmes, E. C. ( 1999; ). Genealogical evidence for positive selection in the nef gene of HIV-1. Genetics 153, 1077–1089.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80510-0
Loading
/content/journal/jgv/10.1099/vir.0.80510-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error