1887

Abstract

Zoonosis of chimpanzee simian immunodeficiency virus cpz to humans has given rise to both pandemic (M) and non-pandemic (O, N and P) groups of human immunodeficiency virus type-1 (HIV). These lentiviruses encode accessory proteins, including Vpu, which has been shown to reduce CD4 levels on the cell surface, as well as increase virion release from the cell by antagonizing tetherin (CD317, BST2). Here, we confirm that O group Vpus (Ca9 and BCF06) are unable to counteract tetherin or downregulate the protein from the cell surface, although they are still able to reduce cell-surface CD4 levels. We hypothesize that this inability to antagonize tetherin may have contributed to O group viruses failing to achieve pandemic levels of human-to-human transmission. Characterization of chimeric O/M group Vpus and Vpu mutants demonstrate that the Vpu–tetherin interaction is complex, involving several domains. We identify specific residues within the transmembrane proximal region that, along with the transmembrane domain, are crucial for tetherin counteraction and enhanced virion release. We have also shown that the critical domains are responsible for the localization of M group Vpu to the -Golgi network, where it relocalizes tetherin to counteract its function. This work sheds light on the acquisition of anti-tetherin activity and the molecular details of pandemic HIV infection in humans.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.035931-0
2011-12-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/12/2937.html?itemId=/content/journal/jgv/10.1099/vir.0.035931-0&mimeType=html&fmt=ahah

References

  1. Cao H., Thompson H. M., Krueger E. W., McNiven M. A. 2000; Disruption of Golgi structure and function in mammalian cells expressing a mutant dynamin. J Cell Sci 113:1993–2002[PubMed]
    [Google Scholar]
  2. Carreno S., Engqvist-Goldstein A. E., Zhang C. X., McDonald K. L., Drubin D. G. 2004; Actin dynamics coupled to clathrin-coated vesicle formation at the trans-Golgi network. J Cell Biol 165:781–788 [View Article][PubMed]
    [Google Scholar]
  3. Dubé M., Roy B. B., Guiot-Guillain P., Mercier J., Binette J., Leung G., Cohen E. A. 2009; Suppression of Tetherin-restricting activity upon human immunodeficiency virus type 1 particle release correlates with localization of Vpu in the trans-Golgi network. J Virol 83:4574–4590 [View Article][PubMed]
    [Google Scholar]
  4. Dunn K. W., Kamocka M. M., McDonald J. H. 2011; A practical guide to evaluating colocalization in biological microscopy. Am J Physiol Cell Physiol 300:C723–C742 [View Article][PubMed]
    [Google Scholar]
  5. Gao F., Bailes E., Robertson D. L., Chen Y., Rodenburg C. M., Michael S. F., Cummins L. B., Arthur L. O., Peeters M. et al.& other authors ( 1999; Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes . Nature 397:436–441 [View Article][PubMed]
    [Google Scholar]
  6. Goffinet C., Allespach I., Homann S., Tervo H. M., Habermann A., Rupp D., Oberbremer L., Kern C., Tibroni N. et al.& other authors ( 2009; HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor. Cell Host Microbe 5:285–297 [View Article][PubMed]
    [Google Scholar]
  7. Gupta R. K., Towers G. J. 2009; A tail of tetherin: how pandemic HIV-1 conquered the world. Cell Host Microbe 6:393–395 [View Article][PubMed]
    [Google Scholar]
  8. Gupta R. K., Hué S., Schaller T., Verschoor E., Pillay D., Towers G. J. 2009a; Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. PLoS Pathog 5:e1000443 [View Article][PubMed]
    [Google Scholar]
  9. Gupta R. K., Mlcochova P., Pelchen-Matthews A., Petit S. J., Mattiuzzo G., Pillay D., Takeuchi Y., Marsh M., Towers G. J. 2009b; Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proc Natl Acad Sci U S A 106:20889–20894 [View Article][PubMed]
    [Google Scholar]
  10. Hauser H., Lopez L. A., Yang S. J., Oldenburg J. E., Exline C. M., Guatelli J. C., Cannon P. M. 2010; HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinuclear compartment. Retrovirology 7:51 [View Article][PubMed]
    [Google Scholar]
  11. Iwabu Y., Fujita H., Kinomoto M., Kaneko K., Ishizaka Y., Tanaka Y., Sata T., Tokunaga K. 2009; HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. J Biol Chem 284:35060–35072 [View Article][PubMed]
    [Google Scholar]
  12. Janssens W., Heyndrickx L., Van der Auwera G., Nkengasong J., Beirnaert E., Vereecken K., Coppens S., Willems B., Fransen K. et al.& other authors ( 1999; Interpatient genetic variability of HIV-1 group O. AIDS 13:41–48 [View Article][PubMed]
    [Google Scholar]
  13. Jia B., Serra-Moreno R., Neidermyer W., Rahmberg A., Mackey J., Fofana I. B., Johnson W. E., Westmoreland S., Evans D. T. 2009; Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS Pathog 5:e1000429 [View Article][PubMed]
    [Google Scholar]
  14. Klimkait T., Strebel K., Hoggan M. D., Martin M. A., Orenstein J. M. 1990; The human immunodeficiency virus type 1-specific protein Vpu is required for efficient virus maturation and release. J Virol 64:621–629[PubMed]
    [Google Scholar]
  15. Kobayashi T., Ode H., Yoshida T., Sato K., Gee P., Yamamoto S. P., Ebina H., Strebel K., Sato H., Koyanagi Y. 2011; Identification of amino acids in the human tetherin transmembrane domain responsible for HIV-1 Vpu interaction and susceptibility. J Virol 85:932–945 [View Article][PubMed]
    [Google Scholar]
  16. Kupzig S., Korolchuk V., Rollason R., Sugden A., Wilde A., Banting G. 2003; Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic 4:694–709 [View Article][PubMed]
    [Google Scholar]
  17. Lemey P., Pybus O. G., Rambaut A., Drummond A. J., Robertson D. L., Roques P., Worobey M., Vandamme A. M. 2004; The molecular population genetics of HIV-1 group O. Genetics 167:1059–1068 [View Article][PubMed]
    [Google Scholar]
  18. Le Tortorec A., Neil S. J. 2009; Antagonism to and intracellular sequestration of human tetherin by the human immunodeficiency virus type 2 envelope glycoprotein. J Virol 83:11966–11978 [View Article][PubMed]
    [Google Scholar]
  19. Lim E. S., Malik H. S., Emerman M. 2010; Ancient adaptive evolution of tetherin shaped the functions of Vpu and Nef in human immunodeficiency virus and primate lentiviruses. J Virol 84:7124–7134 [View Article][PubMed]
    [Google Scholar]
  20. Loussert-Ajaka I., Chaix M. L., Korber B., Letourneur F., Gomas E., Allen E., Ly T. D., Brun-Vézinet F., Simon F., Saragosti S. 1995; Variability of human immunodeficiency virus type 1 group O strains isolated from Cameroonian patients living in France. J Virol 69:5640–5649[PubMed]
    [Google Scholar]
  21. Malim M. H., Emerman M. 2008; HIV-1 accessory proteins – ensuring viral survival in a hostile environment. Cell Host Microbe 3:388–398 [View Article][PubMed]
    [Google Scholar]
  22. Manders E., Verbeek F., Aten J. 1993; Measurement of colocalization of objects in dual-color confocal images. J Microsc 169:375–382 [View Article]
    [Google Scholar]
  23. Mangeat B., Gers-Huber G., Lehmann M., Zufferey M., Luban J., Piguet V. 2009; HIV-1 Vpu neutralizes the antiviral factor tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog 5:e1000574 [View Article][PubMed]
    [Google Scholar]
  24. Margottin F., Bour S. P., Durand H., Selig L., Benichou S., Richard V., Thomas D., Strebel K., Benarous R. 1998; A novel human WD protein, h-β TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol Cell 1:565–574 [View Article][PubMed]
    [Google Scholar]
  25. Martin-Serrano J., Neil S. J. 2011; Host factors involved in retroviral budding and release. Nat Rev Microbiol 9:519–531 [View Article][PubMed]
    [Google Scholar]
  26. McNatt M. W., Zang T., Hatziioannou T., Bartlett M., Fofana I. B., Johnson W. E., Neil S. J., Bieniasz P. D. 2009; Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants. PLoS Pathog 5:e1000300 [View Article][PubMed]
    [Google Scholar]
  27. Neil S. J., Zang T., Bieniasz P. D. 2008; Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425–430 [View Article][PubMed]
    [Google Scholar]
  28. Ruiz A., Hill M. S., Schmitt K., Guatelli J., Stephens E. B. 2008; Requirements of the membrane proximal tyrosine and dileucine-based sorting signals for efficient transport of the subtype C Vpu protein to the plasma membrane and in virus release. Virology 378:58–68 [View Article][PubMed]
    [Google Scholar]
  29. Sauter D., Schindler M., Specht A., Landford W. N., Münch J., Kim K. A., Votteler J., Schubert U., Bibollet-Ruche F., Keele B. F. 2009; Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe 6:409–421 [View Article][PubMed]
    [Google Scholar]
  30. Serra-Moreno R., Jia B., Breed M., Alvarez X., Evans D. T. 2011; Compensatory changes in the cytoplasmic tail of gp41 confer resistance to tetherin/BST-2 in a pathogenic Nef-deleted SIV. Cell Host Microbe 9:46–57 [View Article][PubMed]
    [Google Scholar]
  31. Skasko M., Tokarev A., Chen C. C., Fischer W. B., Pillai S. K., Guatelli J. 2011; BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: evidence for a post-ER mechanism of Vpu-action. Virology 411:65–77 [View Article][PubMed]
    [Google Scholar]
  32. Tokarev A. A., Munguia J., Guatelli J. C. 2011; Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu. J Virol 85:51–63 [View Article][PubMed]
    [Google Scholar]
  33. Van Damme N., Goff D., Katsura C., Jorgenson R. L., Mitchell R., Johnson M. C., Stephens E. B., Guatelli J. 2008; The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3:245–252 [View Article][PubMed]
    [Google Scholar]
  34. Varthakavi V., Smith R. M., Martin K. L., Derdowski A., Lapierre L. A., Goldenring J. R., Spearman P. 2006; The pericentriolar recycling endosome plays a key role in Vpu-mediated enhancement of HIV-1 particle release. Traffic 7:298–307 [View Article][PubMed]
    [Google Scholar]
  35. Willey R. L., Maldarelli F., Martin M. A., Strebel K. 1992; Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol 66:7193–7200[PubMed]
    [Google Scholar]
  36. Zhang F., Wilson S. J., Landford W. C., Virgen B., Gregory D., Johnson M. C., Munch J., Kirchhoff F., Bieniasz P. D., Hatziioannou T. 2009; Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe 6:54–67 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.035931-0
Loading
/content/journal/jgv/10.1099/vir.0.035931-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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