1887

Abstract

An internal RNA loop, located within the packaging signal of human immunodeficiency virus 1, that resembles the Rev-responsive element (RRE) closely was identified previously. Subsequent studies confirmed that the loop, termed loop A, could bind Rev protein specifically. Its proximity to the major splice donor has suggested a role for Rev–loop A interaction supplementary to or preceding that of the Rev–RRE interaction. To investigate this further in a replication-competent provirus, loop A was mutated to decrease its affinity for Rev. Impairing the Rev–loop A interaction led to reduced nuclear export of viral genomic RNA. RNA packaging decreased by approximately 30 %. Viral protein production and export of virus particles appeared normal; however, the virus was severely replication-deficient. The loop A sequence, which is 98 % conserved amongst viral isolates, is implicated in several -acting functions critical to virus viability.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81658-0
2006-10-01
2021-05-09
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/10/3039.html?itemId=/content/journal/jgv/10.1099/vir.0.81658-0&mimeType=html&fmt=ahah

References

  1. Cullen B. R. 1992; Mechanism of action of regulatory proteins encoded by complex retroviruses. Microbiol Rev 56:375–394
    [Google Scholar]
  2. Cullen B. R. 1998; Posttranscriptional regulation by the HIV-1 Rev protein. Semin Virol 8:327–334 [CrossRef]
    [Google Scholar]
  3. D'Agostino D. M., Felber B. K., Harrison J. E., Pavlakis G. N. 1992; The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag / pol and vpu / env mRNAs. Mol Cell Biol 12:1375–1386
    [Google Scholar]
  4. Dangerfield J. A., Hohenadl C., Egerbacher M., Kodajova P., Salmons B., Günzburg W. H. 2005; HIV-1 Rev can specifically interact with MMTV RNA and upregulate gene expression. Gene 358:17–30 [CrossRef]
    [Google Scholar]
  5. Dorman N., Lever A. 2000; Comparison of viral genomic RNA sorting mechanisms in human immunodeficiency virus type 1 (HIV-1), HIV-2, and Moloney murine leukemia virus. J Virol 74:11413–11417 [CrossRef]
    [Google Scholar]
  6. Fisher A. G., Collalti E., Ratner L., Gallo R. C., Wong-Staal F. 1985; A molecular clone of HTLV-III with biological activity. Nature 316:262–265 [CrossRef]
    [Google Scholar]
  7. Gallego J., Greatorex J., Zhang H. & 7 other authors 2003; Rev binds specifically to a purine loop in the SL1 region of the HIV-1 leader RNA. J Biol Chem 278:40385–40391 [CrossRef]
    [Google Scholar]
  8. Greatorex J., Gallego J., Varani G., Lever A. 2002; Structure and stability of wild-type and mutant RNA internal loops from the SL-1 domain of the HIV-1 packaging signal. J Mol Biol 322:543–557 [CrossRef]
    [Google Scholar]
  9. Harrison G. P., Miele G., Hunter E., Lever A. M. L. 1998; Functional analysis of the core human immunodeficiency virus type 1 packaging signal in a permissive cell line. J Virol 72:5886–5896
    [Google Scholar]
  10. Kaye J. F., Lever A. M. L. 1996; trans -Acting proteins involved in RNA encapsidation and viral assembly in human immunodeficiency virus type 1. J Virol 70:880–886
    [Google Scholar]
  11. Kaye J. F., Richardson J. H., Lever A. M. L. 1995; cis -Acting sequences involved in human immunodeficiency virus type 1 RNA packaging. J Virol 69:6588–6592
    [Google Scholar]
  12. Laughrea M., Jette L. 1994; A 19-nucleotide sequence upstream of the 5′ major splice donor is part of the dimerization domain of human immunodeficiency virus 1 genomic RNA. Biochemistry 33:13464–13474 [CrossRef]
    [Google Scholar]
  13. Poole E., Strappe P., Mok H.-P., Hicks R., Lever A. M. L. 2005; HIV-1 Gag–RNA interaction occurs at a perinuclear/centrosomal site; analysis by confocal microscopy and FRET. Traffic 6:741–755 [CrossRef]
    [Google Scholar]
  14. Potts B. 1990; ‘Mini’ reverse transcriptase (RT) assay. In Techniques in HIV Research pp  103–106 Edited by Aldovini A., Walker B. D. New York: Stockton Press;
    [Google Scholar]
  15. Skripkin E., Paillart J.-C., Marquet R., Ehresmann B., Ehresmann C. 1994; Identification of the primary site of the human immunodeficiency virus type 1 RNA dimerization in vitro . Proc Natl Acad Sci U S A 91:4945–4949 [CrossRef]
    [Google Scholar]
  16. Swanson C. M., Puffer B. A., Ahmad K. M., Doms R. W., Malim M. H. 2004; Retroviral mRNA nuclear export elements regulate protein function and virion assembly. EMBO J 23:2632–2640 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81658-0
Loading
/content/journal/jgv/10.1099/vir.0.81658-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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