1887

Abstract

The Rev protein of human immunodeficiency viruses (HIV) has long been recognized to be essential for the late phase of the virus replication cycle, due to its strong enhancement of expression of viral structural proteins. Surprisingly, a number of recent papers have demonstrated that Rev can also interfere with integration of the reverse-transcribed cDNA into the host-cell genome. This seems to be due to Rev's binding to integrase and LEDGF/p75, an important cellular cofactor of HIV-1 integration. As Rev is presumably expressed at sufficiently high levels only after the encoding genome has already integrated, the main function of Rev during the early phase might be to reduce genotoxicity due to excessive integration events after superinfection of the same cell by subsequent viruses. Other potential consequences for HIV-1 replication and evolution after co-infection of the same cell with two viruses are discussed.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.022509-0
2010-08-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/8/1893.html?itemId=/content/journal/jgv/10.1099/vir.0.022509-0&mimeType=html&fmt=ahah

References

  1. Blackard J. T., Cohen D. E., Mayer K. H. 2002; Human immunodeficiency virus superinfection and recombination: current state of knowledge and potential clinical consequences. Clin Infect Dis 34:1108–1114
    [Google Scholar]
  2. Blissenbach M., Grewe B., Hoffmann B., Brandt S., Überla K. 2010; Nuclear RNA export and packaging functions of HIV-1 Rev revisited. J Virol 84:6598–6604
    [Google Scholar]
  3. Bocharov G., Ford N. J., Edwards J., Breinig T., Wain-Hobson S., Meyerhans A. 2005; A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination. J Gen Virol 86:3109–3118
    [Google Scholar]
  4. Brandt S., Blissenbach M., Grewe B., Konietzny R., Grunwald T., Überla K. 2007; Rev proteins of human and simian immunodeficiency virus enhance RNA encapsidation. PLoS Pathog 3:e54
    [Google Scholar]
  5. Burke D. S. 1997; Recombination in HIV: an important viral evolutionary strategy. Emerg Infect Dis 3:253–259
    [Google Scholar]
  6. Butler S. L., Hansen M. S., Bushman F. D. 2001; A quantitative assay for HIV DNA integration in vivo . Nat Med 7:631–634
    [Google Scholar]
  7. Engelman A., Cherepanov P. 2008; The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS Pathog 4:e1000046
    [Google Scholar]
  8. Fox C. H., Tenner-Racz K., Racz P., Firpo A., Pizzo P. A., Fauci A. S. 1991; Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA. J Infect Dis 164:1051–1057
    [Google Scholar]
  9. Freed E. O. 2001; HIV-1 replication. Somat Cell Mol Genet 26:13–33
    [Google Scholar]
  10. Gelderblom H. C., Vatakis D. N., Burke S. A., Lawrie S. D., Bristol G. C., Levy D. N. 2008; Viral complementation allows HIV-1 replication without integration. Retrovirology 5:60
    [Google Scholar]
  11. Gratton S., Cheynier R., Dumaurier M. J., Oksenhendler E., Wain-Hobson S. 2000; Highly restricted spread of HIV-1 and multiply infected cells within splenic germinal centers. Proc Natl Acad Sci U S A 97:14566–14571
    [Google Scholar]
  12. Grewe B., Überla K. 2010 Rev revisited: additional functions of the HIV-1 Rev protein. In Recent Advances in Human Retroviruses: Principles of Replication and Pathogenesis , chapter 14 Edited by Lever A. M. L., Jeang K. T., Berkhout. New Jersey, London, Singapore: World Scientific Publishing; (in press)
    [Google Scholar]
  13. Groom H. C., Anderson E. C., Lever A. M. 2009; Rev: beyond nuclear export. J Gen Virol 90:1303–1318
    [Google Scholar]
  14. Hayouka Z., Rosenbluh J., Levin A., Maes M., Loyter A., Friedler A. 2008; Peptides derived from HIV-1 Rev inhibit HIV-1 integrase in a shiftide mechanism. Biopolymers 90:481–487
    [Google Scholar]
  15. Jolly C., Sattentau Q. J. 2004; Retroviral spread by induction of virological synapses. Traffic 5:643–650
    [Google Scholar]
  16. Jolly C., Kashefi K., Hollinshead M., Sattentau Q. J. 2004; HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med 199:283–293
    [Google Scholar]
  17. Levesque K., Finzi A., Binette J., Cohen E. A. 2004; Role of CD4 receptor down-regulation during HIV-1 infection. Curr HIV Res 2:51–59
    [Google Scholar]
  18. Levin A., Hayouka Z., Brack-Werner R., Volsky D. J., Friedler A., Loyter A. 2009a; Novel regulation of HIV-1 replication and pathogenicity: Rev inhibition of integration. Protein Eng Des Sel 22:753–763
    [Google Scholar]
  19. Levin A., Hayouka Z., Helfer M., Brack-Werner R., Friedler A., Loyter A. 2009b; Peptides derived from HIV-1 integrase that bind Rev stimulate viral genome integration. PLoS One 4:e4155
    [Google Scholar]
  20. Levin A., Rosenbluh J., Hayouka Z., Friedler A., Loyter A. 2010a; Integration of HIV-1 DNA is regulated by interplay between viral rev and cellular LEDGF/p75 proteins. Mol Med 16:34–44
    [Google Scholar]
  21. Levin A., Hayouka Z., Friedler A., Brack-Werner R., Volsky D. J., Loyter A. 2010b; A novel role for the viral Rev protein in promoting resistance to superinfection by human immunodeficiency virus type 1. J Gen Virol 91:1503–1513
    [Google Scholar]
  22. Lindwasser O. W., Chaudhuri R., Bonifacino J. S. 2007; Mechanisms of CD4 downregulation by the Nef and Vpu proteins of primate immunodeficiency viruses. Curr Mol Med 7:171–184
    [Google Scholar]
  23. Malim M. H., Emerman M. 2008; HIV-1 accessory proteins – ensuring viral survival in a hostile environment. Cell Host Microbe 3:388–398
    [Google Scholar]
  24. McDonald D., Wu L., Bohks S. M., KewalRamani V. N., Unutmaz D., Hope T. J. 2003; Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science 300:1295–1297
    [Google Scholar]
  25. Najera R., Delgado E., Perez-Alvarez L., Thomson M. M. 2002; Genetic recombination and its role in the development of the HIV-1 pandemic. AIDS 16:Suppl. 4S3–S16
    [Google Scholar]
  26. Nekhai S., Jeang K. T. 2006; Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev. Future Microbiol 1:417–426
    [Google Scholar]
  27. Nethe M., Berkhout B., van der Kuyl A. C. 2005; Retroviral superinfection resistance. Retrovirology 2:52
    [Google Scholar]
  28. Rosenbluh J., Hayouka Z., Loya S., Levin A., Armon-Omer A., Britan E., Hizi A., Kotler M., Friedler A. other authors 2007; Interaction between HIV-1 Rev and integrase proteins: a basis for the development of anti-HIV peptides. J Biol Chem 282:15743–15753
    [Google Scholar]
  29. Wagner R., Matrosovich M., Klenk H. D. 2002; Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol 12:159–166
    [Google Scholar]
  30. Wu Y. 2004; HIV-1 gene expression: lessons from provirus and non-integrated DNA. Retrovirology 1:13
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.022509-0
Loading
/content/journal/jgv/10.1099/vir.0.022509-0
Loading

Data & Media loading...

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