This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dettenhofer, M.
Right arrow Articles by Yu, X.-F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dettenhofer, M.
Right arrow Articles by Yu, X.-F.

 Previous Article  |  Next Article 

Journal of Virology, June 1999, p. 4696-4704, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Proline Residues in Human Immunodeficiency Virus Type 1 p6Gag Exert a Cell Type-Dependent Effect on Viral Replication and Virion Incorporation of Pol Proteins

Markus Dettenhofer and Xiao-Fang Yu*

Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205

Received 20 October 1998/Accepted 13 February 1999

The C terminus of the HIV-1 Gag protein contains a proline-rich domain termed p6Gag. This domain has been shown to play a role in efficient virus release and incorporation of Vpr into virions. In a previous study (X. F. Yu, L. Dawson, C. J. Tian, C. Flexner, and M. Dettenhofer, J. Virol. 72:3412-3417, 1998), we observed that the removal of the p6 domain of Gag as well as drastic mutations in the PTAP motif resulted in reduced virion-associated Pol proteins from transfected COS cells. In the present study, amino acid substitutions at residues 5 and 7 of p6Gag resulted in a cell type-dependent replication of the mutant virus in CD4+ T cells; the virus was replication competent in Jurkat cells but restricted in H9 cells and primary blood-derived monocytes. Established Jurkat and H9 cell lines expressing p6Gag mutant and parental virus were used to further understand this defect. Mutant virions produced from H9 cells, which displayed no defect in extracellular virion production, showed an ~16-fold reduction in Pol protein levels, whereas the levels of Pol proteins were only marginally reduced in mutant virions produced from Jurkat cells. The reduction in the virion-associated Pol proteins could not be accounted for by differences in the levels of intracellular p160Gag-Pol or in the interaction between p55Gag and p160Gag-Pol precursors. Electron microscopic analysis of the p6Gag mutant virions showed a predominately immature morphology in the absence of significant defects in Gag proteolytic cleavage. Taken together, these data suggest that the proline-rich motif of p6Gag is involved in the late stages of virus maturation, which include the packaging of cleaved Pol proteins in viral particles, a process which may involve cell-type-specific factors.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Hygiene and Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3768. Fax: (410) 614-8263. E-mail: xfyu{at}jhsph.edu.

Journal of Virology, June 1999, p. 4696-4704, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Dykes, C., Demeter, L. M. (2007). Clinical Significance of Human Immunodeficiency Virus Type 1 Replication Fitness. Clin. Microbiol. Rev. 20: 550-578 [Abstract] [Full Text]  
  • Neumann, G., Ebihara, H., Takada, A., Noda, T., Kobasa, D., Jasenosky, L. D., Watanabe, S., Kim, J. H., Feldmann, H., Kawaoka, Y. (2005). Ebola Virus VP40 Late Domains Are Not Essential for Viral Replication in Cell Culture. J. Virol. 79: 10300-10307 [Abstract] [Full Text]  
  • Hemonnot, B., Cartier, C., Gay, B., Rebuffat, S., Bardy, M., Devaux, C., Boyer, V., Briant, L. (2004). The Host Cell MAP Kinase ERK-2 Regulates Viral Assembly and Release by Phosphorylating the p6gag Protein of HIV-1. J. Biol. Chem. 279: 32426-32434 [Abstract] [Full Text]  
  • Bleiber, G., Peters, S., Martinez, R., Cmarko, D., Meylan, P., Telenti, A. (2004). The central region of human immunodeficiency virus type 1 p6 protein (Gag residues S14-I31) is dispensable for the virus in vitro. J. Gen. Virol. 85: 921-927 [Abstract] [Full Text]  
  • Cen, S., Niu, M., Saadatmand, J., Guo, F., Huang, Y., Nabel, G. J., Kleiman, L. (2004). Incorporation of Pol into Human Immunodeficiency Virus Type 1 Gag Virus-Like Particles Occurs Independently of the Upstream Gag Domain in Gag-Pol. J. Virol. 78: 1042-1049 [Abstract] [Full Text]  
  • Martin-Serrano, J., Bieniasz, P. D. (2003). A Bipartite Late-Budding Domain in Human Immunodeficiency Virus Type 1. J. Virol. 77: 12373-12377 [Abstract] [Full Text]  
  • Maguire, M. F., Guinea, R., Griffin, P., Macmanus, S., Elston, R. C., Wolfram, J., Richards, N., Hanlon, M. H., Porter, D. J. T., Wrin, T., Parkin, N., Tisdale, M., Furfine, E., Petropoulos, C., Snowden, B. W., Kleim, J.-P. (2002). Changes in Human Immunodeficiency Virus Type 1 Gag at Positions L449 and P453 Are Linked to I50V Protease Mutants In Vivo and Cause Reduction of Sensitivity to Amprenavir and Improved Viral Fitness In Vitro. J. Virol. 76: 7398-7406 [Abstract] [Full Text]  
  • Freed, E. O. (2002). Viral Late Domains. J. Virol. 76: 4679-4687 [Full Text]  
  • Muller, B., Patschinsky, T., Krausslich, H.-G. (2002). The Late-Domain-Containing Protein p6 Is the Predominant Phosphoprotein of Human Immunodeficiency Virus Type 1 Particles. J. Virol. 76: 1015-1024 [Abstract] [Full Text]  
  • Demirov, D. G., Orenstein, J. M., Freed, E. O. (2002). The Late Domain of Human Immunodeficiency Virus Type 1 p6 Promotes Virus Release in a Cell Type-Dependent Manner. J. Virol. 76: 105-117 [Abstract] [Full Text]  
  • Guan, Y., Diallo, K., Detorio, M., Whitney, J. B., Liang, C., Wainberg, M. A. (2001). Partial Restoration of Replication of Simian Immunodeficiency Virus by Point Mutations in either the Dimerization Initiation Site (DIS) or Gag Region after Deletion Mutagenesis within the DIS. J. Virol. 75: 11920-11923 [Abstract] [Full Text]  
  • Peters, S., Munoz, M., Yerly, S., Sanchez-Merino, V., Lopez-Galindez, C., Perrin, L., Larder, B., Cmarko, D., Fakan, S., Meylan, P., Telenti, A. (2001). Resistance to Nucleoside Analog Reverse Transcriptase Inhibitors Mediated by Human Immunodeficiency Virus Type 1 p6 Protein. J. Virol. 75: 9644-9653 [Abstract] [Full Text]  
  • Reichert, M., Winnicka, A., Willems, L., Kettmann, R., Cantor, G. H. (2001). Role of the Proline-Rich Motif of Bovine Leukemia Virus Transmembrane Protein gp30 in Viral Load and Pathogenicity in Sheep. J. Virol. 75: 8082-8089 [Abstract] [Full Text]  
  • VerPlank, L., Bouamr, F., LaGrassa, T. J., Agresta, B., Kikonyogo, A., Leis, J., Carter, C. A. (2001). Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55Gag. Proc. Natl. Acad. Sci. USA 10.1073/pnas.131059198v1 [Abstract] [Full Text]  
  • VerPlank, L., Bouamr, F., LaGrassa, T. J., Agresta, B., Kikonyogo, A., Leis, J., Carter, C. A. (2001). Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55Gag. Proc. Natl. Acad. Sci. USA 98: 7724-7729 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»