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 Huang, L.
Right arrow Articles by Pardee, A. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, L.
Right arrow Articles by Pardee, A. B.

 Previous Article  |  Next Article 

Journal of Virology, November 1998, p. 8952-8960, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Tat Protein Induces Human Immunodeficiency Virus Type 1 (HIV-1) Coreceptors and Promotes Infection with both Macrophage-Tropic and T-Lymphotropic HIV-1 Strains

Lili Huang,1,2,* Irene Bosch,1,2 Wolfgang Hofmann,3,4 Joseph Sodroski,3,4 and Arthur B. Pardee1,2

Divisions of Cancer Biology1 and Human Retrovirology,3 Dana-Farber Cancer Institute, and Departments of Biological Chemistry and Molecular Pharmacology2 and Pathology,4 Harvard Medical School, Boston, Massachusetts 02115

Received 27 May 1998/Accepted 6 August 1998

Chemokine receptors CCR5 and CXCR4 are the primary fusion coreceptors utilized for CD4-mediated entry by macrophage (M)- and T-cell line (T)-tropic human immunodeficiency virus type 1 (HIV-1) strains, respectively. Here we demonstrate that HIV-1 Tat protein, a potent viral transactivator shown to be released as a soluble protein by infected cells, differentially induced CXCR4 and CCR5 expression in peripheral blood mononuclear cells. CCR3, a less frequently used coreceptor for certain M-tropic strains, was also induced. CXCR4 was induced on both lymphocytes and monocytes/macrophages, whereas CCR5 and CCR3 were induced on monocytes/macrophages but not on lymphocytes. The pattern of chemokine receptor induction by Tat was distinct from that by phytohemagglutinin. Moreover, Tat-induced CXCR4 and CCR5 expression was dose dependent. Monocytes/macrophages were more susceptible to Tat-mediated induction of CXCR4 and CCR5 than lymphocytes, and CCR5 was more readily induced than CXCR4. The concentrations of Tat effective in inducing CXCR4 and CCR5 expression were within the picomolar range and close to the range of extracellular Tat observed in sera from HIV-1-infected individuals. The induction of CCR5 and CXCR4 expression correlated with Tat-enhanced infectivity of M- and T-tropic viruses, respectively. Taken together, our results define a novel role for Tat in HIV-1 pathogenesis that promotes the infectivity of both M- and T-tropic HIV-1 strains in primary human leukocytes, notably in monocytes/macrophages.

* Corresponding author. Mailing address: Division of Cancer Biology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Phone: (617) 632-4688. Fax: (617) 632-4680. E-mail: lhuang{at}mbcrr.harvard.edu.

Journal of Virology, November 1998, p. 8952-8960, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Florese, R. H., Demberg, T., Xiao, P., Kuller, L., Larsen, K., Summers, L. E., Venzon, D., Cafaro, A., Ensoli, B., Robert-Guroff, M. (2009). Contribution of Nonneutralizing Vaccine-Elicited Antibody Activities to Improved Protective Efficacy in Rhesus Macaques Immunized with Tat/Env Compared with Multigenic Vaccines. J. Immunol. 182: 3718-3727 [Abstract] [Full Text]  
  • Thacker, T. C., Zhou, X., Estes, J. D., Jiang, Y., Keele, B. F., Elton, T. S., Burton, G. F. (2009). Follicular Dendritic Cells and Human Immunodeficiency Virus Type 1 Transcription in CD4+ T Cells. J. Virol. 83: 150-158 [Abstract] [Full Text]  
  • Demberg, T., Florese, R. H., Heath, M. J., Larsen, K., Kalisz, I., Kalyanaraman, V. S., Lee, E. M., Pal, R., Venzon, D., Grant, R., Patterson, L. J., Korioth-Schmitz, B., Buzby, A., Dombagoda, D., Montefiori, D. C., Letvin, N. L., Cafaro, A., Ensoli, B., Robert-Guroff, M. (2007). A Replication-Competent Adenovirus-Human Immunodeficiency Virus (Ad-HIV) tat and Ad-HIV env Priming/Tat and Envelope Protein Boosting Regimen Elicits Enhanced Protective Efficacy against Simian/Human Immunodeficiency Virus SHIV89.6P Challenge in Rhesus Macaques. J. Virol. 81: 3414-3427 [Abstract] [Full Text]  
  • Mondal, D., Williams, C. A., Ali, M., Eilers, M., Agrawal, K. C. (2005). The HIV-1 Tat Protein Selectively Enhances CXCR4 and Inhibits CCR5 Expression in Megakaryocytic K562 Cells. Exp. Biol. Med. 230: 631-644 [Abstract] [Full Text]  
  • Mascarell, L., Fayolle, C., Bauche, C., Ladant, D., Leclerc, C. (2005). Induction of Neutralizing Antibodies and Th1-Polarized and CD4-Independent CD8+ T-Cell Responses following Delivery of Human Immunodeficiency Virus Type 1 Tat Protein by Recombinant Adenylate Cyclase of Bordetella pertussis. J. Virol. 79: 9872-9884 [Abstract] [Full Text]  
  • Marchio, S., Alfano, M., Primo, L., Gramaglia, D., Butini, L., Gennero, L., De Vivo, E., Arap, W., Giacca, M., Pasqualini, R., Bussolino, F. (2005). Cell surface-associated Tat modulates HIV-1 infection and spreading through a specific interaction with gp120 viral envelope protein. Blood 105: 2802-2811 [Abstract] [Full Text]  
  • Ruckwardt, T. J., Tikhonov, I., Berg, S., Hatfield, G. S., Chandra, A., Chandra, P., Gilliam, B., Redfield, R. R., Gallo, R. C., Pauza, C. D. (2004). Sequence Variation within the Dominant Amino Terminus Epitope Affects Antibody Binding and Neutralization of Human Immunodeficiency Virus Type 1 Tat Protein. J. Virol. 78: 13190-13196 [Abstract] [Full Text]  
  • Estes, J. D., Thacker, T. C., Hampton, D. L., Kell, S. A., Keele, B. F., Palenske, E. A., Druey, K. M., Burton, G. F. (2004). Follicular Dendritic Cell Regulation of CXCR4-Mediated Germinal Center CD4 T Cell Migration. J. Immunol. 173: 6169-6178 [Abstract] [Full Text]  
  • Moreau, E., Belliard, G., Partidos, C. D., Pradezinsky, F., Le Buanec, H., Muller, S., Desgranges, C. (2004). Important B-cell epitopes for neutralization of human immunodeficiency virus type 1 Tat in serum samples of humans and different animal species immunized with Tat protein or peptides. J. Gen. Virol. 85: 2893-2901 [Abstract] [Full Text]  
  • Calzado, M. A., Sancho, R., Munoz, E. (2004). Human Immunodeficiency Virus Type 1 Tat Increases the Expression of Cleavage and Polyadenylation Specificity Factor 73-Kilodalton Subunit Modulating Cellular and Viral Expression. J. Virol. 78: 6846-6854 [Abstract] [Full Text]  
  • Wahl, S. M., Greenwell-Wild, T., Peng, G., Ma, G., Orenstein, J. M., Vazquez, N. (2003). Viral and host cofactors facilitate HIV-1 replication in macrophages. J. Leukoc. Biol. 74: 726-735 [Abstract] [Full Text]  
  • Yang, Y., Tikhonov, I., Ruckwardt, T. J., Djavani, M., Zapata, J. C., Pauza, C. D., Salvato, M. S. (2003). Monocytes Treated with Human Immunodeficiency Virus Tat Kill Uninfected CD4+ Cells by a Tumor Necrosis Factor-Related Apoptosis-Induced Ligand-Mediated Mechanism. J. Virol. 77: 6700-6708 [Abstract] [Full Text]  
  • Tikhonov, I., Ruckwardt, T. J., Hatfield, G. S., Pauza, C. D. (2003). Tat-Neutralizing Antibodies in Vaccinated Macaques. J. Virol. 77: 3157-3166 [Abstract] [Full Text]  
  • Bres, V., Kiernan, R., Emiliani, S., Benkirane, M. (2002). Tat Acetyl-acceptor Lysines Are Important for Human Immunodeficiency Virus Type-1 Replication. J. Biol. Chem. 277: 22215-22221 [Abstract] [Full Text]  
  • Silvera, P., Richardson, M. W., Greenhouse, J., Yalley-Ogunro, J., Shaw, N., Mirchandani, J., Khalili, K., Zagury, J.-F., Lewis, M. G., Rappaport, J. (2002). Outcome of Simian-Human Immunodeficiency Virus Strain 89.6p Challenge following Vaccination of Rhesus Macaques with Human Immunodeficiency Virus Tat Protein. J. Virol. 76: 3800-3809 [Abstract] [Full Text]  
  • Fanales-Belasio, E., Moretti, S., Nappi, F., Barillari, G., Micheletti, F., Cafaro, A., Ensoli, B. (2002). Native HIV-1 Tat Protein Targets Monocyte-Derived Dendritic Cells and Enhances Their Maturation, Function, and Antigen-Specific T Cell Responses. J. Immunol. 168: 197-206 [Abstract] [Full Text]  
  • Arese, M., Ferrandi, C., Primo, L., Camussi, G., Bussolino, F. (2001). HIV-1 Tat Protein Stimulates In Vivo Vascular Permeability and Lymphomononuclear Cell Recruitment. J. Immunol. 166: 1380-1388 [Abstract] [Full Text]  
  • de Paulis, A., De Palma, R., Di Gioia, L., Carfora, M., Prevete, N., Tosi, G., Accolla, R. S., Marone, G. (2000). Tat Protein Is an HIV-1-Encoded {beta}-Chemokine Homolog That Promotes Migration and Up-Regulates CCR3 Expression on Human Fc{epsilon}RI+ Cells. J. Immunol. 165: 7171-7179 [Abstract] [Full Text]  
  • Badou, A., Bennasser, Y., Moreau, M., Leclerc, C., Benkirane, M., Bahraoui, E. (2000). Tat Protein of Human Immunodeficiency Virus Type 1 Induces Interleukin-10 in Human Peripheral Blood Monocytes: Implication of Protein Kinase C-Dependent Pathway. J. Virol. 74: 10551-10562 [Abstract] [Full Text]  
  • Xiao, H., Neuveut, C., Tiffany, H. L., Benkirane, M., Rich, E. A., Murphy, P. M., Jeang, K.-T. (2000). Selective CXCR4 antagonism by Tat: Implications for in vivo expansion of coreceptor use by HIV-1. Proc. Natl. Acad. Sci. USA 97: 11466-11471 [Abstract] [Full Text]  
  • Orsini, M. J., Parent, J.-L., Mundell, S. J., Benovic, J. L. (1999). Trafficking of the HIV Coreceptor CXCR4. ROLE OF ARRESTINS AND IDENTIFICATION OF RESIDUES IN THE C-TERMINAL TAIL THAT MEDIATE RECEPTOR INTERNALIZATION. J. Biol. Chem. 274: 31076-31086 [Abstract] [Full Text]  
  • Weiss, J. M., Nath, A., Major, E. O., Berman, J. W. (1999). HIV-1 Tat Induces Monocyte Chemoattractant Protein-1-Mediated Monocyte Transmigration Across a Model of the Human Blood-Brain Barrier and Up-Regulates CCR5 Expression on Human Monocytes. J. Immunol. 163: 2953-2959 [Abstract] [Full Text]  
  • Gallo, R. C. (1999). Tat as one key to HIV-induced immune pathogenesis and Pat toxoid as an important component of a vaccine. Proc. Natl. Acad. Sci. USA 96: 8324-8326 [Full Text]  
  • Caselli, E., Betti, M., Grossi, M. P., Balboni, P. G., Rossi, C., Boarini, C., Cafaro, A., Barbanti-Brodano, G., Ensoli, B., Caputo, A. (1999). DNA Immunization with HIV-1 tat Mutated in the trans Activation Domain Induces Humoral and Cellular Immune Responses Against Wild-Type Tat. J. Immunol. 162: 5631-5638 [Abstract] [Full Text]  
  • Pauza, C. D., Trivedi, P., Wallace, M., Ruckwardt, T. J., Le Buanec, H., Lu, W., Bizzini, B., Burny, A., Zagury, D., Gallo, R. C. (2000). Vaccination with Tat toxoid attenuates disease in simian/HIV-challenged macaques. Proc. Natl. Acad. Sci. USA 97: 3515-3519 [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»