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 Li, J.
Right arrow Articles by He, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, J.
Right arrow Articles by He, J. J.

 Previous Article  |  Next Article 

Journal of Virology, August 2002, p. 8374-8382, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8374-8382.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Direct Participation of Sam68, the 68-Kilodalton Src-Associated Protein in Mitosis, in the CRM1-Mediated Rev Nuclear Export Pathway

Jinliang Li,1,2 Ying Liu,1,2 Byung Oh Kim,1,2 and Johnny J. He1,2,3,4*

Department of Microbiology and Immunology,1 Walther Oncology Center,2 Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202,3 Walther Cancer Institute, Indianapolis, Indiana 462084

Received 29 January 2002/ Accepted 8 May 2002

Human immunodeficiency virus type 1 (HIV-1) replication requires efficient nuclear export of incompletely spliced and unspliced HIV-1 mRNA transcripts, which is achieved by Rev expression at an early stage of the viral life cycle. We have recently shown that expression of Sam68, the 68-kDa Src-associated protein in mitosis, is able to alleviate Rev function block in astrocytes by promoting Rev nuclear export. In the present study, we utilized an antisense RNA expression strategy to down-modulate constitutive Sam68 expression and examined its effect on Rev function, HIV-1 gene expression, and viral replication. These results showed that down-modulation of constitutive Sam68 expression markedly inhibited HIV-1 production in 293T cells and viral replication in T lymphocytes such as Jurkat and CEM cells, as well as human peripheral blood mononuclear cells (PBMCs). Rev-dependent in trans complementation and reporter gene assays further demonstrated that inhibition of HIV-1 gene expression by Sam68 down-modulation was due to impeded Rev activity. Moreover, digital fluorescence microscopic imaging revealed that down-modulation of Sam68 expression caused exclusive nuclear retention and colocalization of both Rev and CRM1. Taken together, these data suggest that adequate Sam68 expression is required for Rev function and, thereby, for HIV-1 gene expression and viral replication, and they support the notion that Sam68 is directly involved in the CRM1-mediated Rev nuclear export pathway.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Indiana University School of Medicine, R4 302, 1044 W. Walnut St., Indianapolis, IN 46202. Phone: (317) 274-7525. Fax: (317) 274-7592. E-mail: jjhe{at}iupui.edu.

Journal of Virology, August 2002, p. 8374-8382, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8374-8382.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Groom, H. C. T., Anderson, E. C., Lever, A. M. L. (2009). Rev: beyond nuclear export. J. Gen. Virol. 90: 1303-1318 [Abstract] [Full Text]  
  • Paronetto, M. P., Messina, V., Bianchi, E., Barchi, M., Vogel, G., Moretti, C., Palombi, F., Stefanini, M., Geremia, R., Richard, S., Sette, C. (2009). Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis. JCB 185: 235-249 [Abstract] [Full Text]  
  • Huot, M.-E., Brown, C. M., Lamarche-Vane, N., Richard, S. (2009). An Adaptor Role for Cytoplasmic Sam68 in Modulating Src Activity during Cell Polarization. Mol. Cell. Biol. 29: 1933-1943 [Abstract] [Full Text]  
  • Carroll-Anzinger, D., Kumar, A., Adarichev, V., Kashanchi, F., Al-Harthi, L. (2007). Human Immunodeficiency Virus-Restricted Replication in Astrocytes and the Ability of Gamma Interferon To Modulate This Restriction Are Regulated by a Downstream Effector of the Wnt Signaling Pathway. J. Virol. 81: 5864-5871 [Abstract] [Full Text]  
  • Paronetto, M. P., Zalfa, F., Botti, F., Geremia, R., Bagni, C., Sette, C. (2006). The Nuclear RNA-binding Protein Sam68 Translocates to the Cytoplasm and Associates with the Polysomes in Mouse Spermatocytes. Mol. Biol. Cell 17: 14-24 [Abstract] [Full Text]  
  • Zhang, J., Li, G., Bafica, A., Pantelic, M., Zhang, P., Broxmeyer, H., Liu, Y., Wetzler, L., He, J. J., Chen, T. (2005). Neisseria gonorrhoeae Enhances Infection of Dendritic Cells by HIV Type 1. J. Immunol. 174: 7995-8002 [Abstract] [Full Text]  
  • Haegebarth, A., Heap, D., Bie, W., Derry, J. J., Richard, S., Tyner, A. L. (2004). The Nuclear Tyrosine Kinase BRK/Sik Phosphorylates and Inhibits the RNA-binding Activities of the Sam68-like Mammalian Proteins SLM-1 and SLM-2. J. Biol. Chem. 279: 54398-54404 [Abstract] [Full Text]  
  • MCLAREN, M., ASAI, K., COCHRANE, A. (2004). A novel function for Sam68: Enhancement of HIV-1 RNA 3' end processing. RNA 10: 1119-1129 [Abstract] [Full Text]  
  • Liu, Y., Liu, H., Kim, B. O., Gattone, V. H., Li, J., Nath, A., Blum, J., He, J. J. (2004). CD4-Independent Infection of Astrocytes by Human Immunodeficiency Virus Type 1: Requirement for the Human Mannose Receptor. J. Virol. 78: 4120-4133 [Abstract] [Full Text]  
  • Fredj, N. B., Grange, J., Sadoul, R., Richard, S., Goldberg, Y., Boyer, V. (2004). Depolarization-induced translocation of the RNA-binding protein Sam68 to the dendrites of hippocampal neurons. J. Cell Sci. 117: 1079-1090 [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»