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The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production.
J Virol. 2007 Mar; 81(6):2909-22.JV

Abstract

The human immunodeficiency virus type 1 (HIV-1) Gag protein recruits Tsg101 to facilitate HIV-1 particle budding and release. In uninfected cells, the Hrs protein recruits the ESCRT-I complex to the endosome, also through an interaction with Tsg101, to promote the sorting of host proteins into endosomal vesicles and multivesicular bodies. Here, we show that the overexpression of the C-terminal fragment of Hrs (residues 391 to 777) or Hrs mutants lacking either the N-terminal FYVE domain (mutant dFYVE) or the PSAP (residues 348 to 351) motif (mutant ASAA) all efficiently inhibit HIV-1 Gag particle production. Expression of the dFYVE or ASAA mutants of Hrs had no effect on the release of Moloney murine leukemia virus. Coimmunoprecipitation analysis showed that the expression of Hrs mutant dFYVE or ASAA significantly reduced or abolished the HIV-1 Gag-Tsg101 interaction. Yeast-two hybrid assays were used to identify two new and independent Tsg101 binding sites, one in the Hrs coiled-coil domain and one in the proline/glutamic acid-rich domain. Scanning electron microscopy of HeLa cells expressing HIV-1 Gag and the Hrs ASAA mutant showed viral particles arrested in "lump-like" structures that remained attached to the cell surface. Together, these data indicate that fragments of Hrs containing the C-terminal portion of the protein can potently inhibit HIV-1 particle release by efficiently sequestering Tsg101 away from the Gag polyprotein.

Authors+Show Affiliations

Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17182674

Citation

Bouamr, Fadila, et al. "The C-terminal Portion of the Hrs Protein Interacts With Tsg101 and Interferes With Human Immunodeficiency Virus Type 1 Gag Particle Production." Journal of Virology, vol. 81, no. 6, 2007, pp. 2909-22.
Bouamr F, Houck-Loomis BR, De Los Santos M, et al. The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production. J Virol. 2007;81(6):2909-22.
Bouamr, F., Houck-Loomis, B. R., De Los Santos, M., Casaday, R. J., Johnson, M. C., & Goff, S. P. (2007). The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production. Journal of Virology, 81(6), 2909-22.
Bouamr F, et al. The C-terminal Portion of the Hrs Protein Interacts With Tsg101 and Interferes With Human Immunodeficiency Virus Type 1 Gag Particle Production. J Virol. 2007;81(6):2909-22. PubMed PMID: 17182674.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production. AU - Bouamr,Fadila, AU - Houck-Loomis,Brian R, AU - De Los Santos,Martha, AU - Casaday,Rebecca J, AU - Johnson,Marc C, AU - Goff,Stephen P, Y1 - 2006/12/20/ PY - 2006/12/22/pubmed PY - 2007/4/5/medline PY - 2006/12/22/entrez SP - 2909 EP - 22 JF - Journal of virology JO - J. Virol. VL - 81 IS - 6 N2 - The human immunodeficiency virus type 1 (HIV-1) Gag protein recruits Tsg101 to facilitate HIV-1 particle budding and release. In uninfected cells, the Hrs protein recruits the ESCRT-I complex to the endosome, also through an interaction with Tsg101, to promote the sorting of host proteins into endosomal vesicles and multivesicular bodies. Here, we show that the overexpression of the C-terminal fragment of Hrs (residues 391 to 777) or Hrs mutants lacking either the N-terminal FYVE domain (mutant dFYVE) or the PSAP (residues 348 to 351) motif (mutant ASAA) all efficiently inhibit HIV-1 Gag particle production. Expression of the dFYVE or ASAA mutants of Hrs had no effect on the release of Moloney murine leukemia virus. Coimmunoprecipitation analysis showed that the expression of Hrs mutant dFYVE or ASAA significantly reduced or abolished the HIV-1 Gag-Tsg101 interaction. Yeast-two hybrid assays were used to identify two new and independent Tsg101 binding sites, one in the Hrs coiled-coil domain and one in the proline/glutamic acid-rich domain. Scanning electron microscopy of HeLa cells expressing HIV-1 Gag and the Hrs ASAA mutant showed viral particles arrested in "lump-like" structures that remained attached to the cell surface. Together, these data indicate that fragments of Hrs containing the C-terminal portion of the protein can potently inhibit HIV-1 particle release by efficiently sequestering Tsg101 away from the Gag polyprotein. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/17182674/The_C_terminal_portion_of_the_Hrs_protein_interacts_with_Tsg101_and_interferes_with_human_immunodeficiency_virus_type_1_Gag_particle_production_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=17182674 DB - PRIME DP - Unbound Medicine ER -