This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
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 Arthos, J.
Right arrow Articles by Fauci, A. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arthos, J.
Right arrow Articles by Fauci, A. S.

 Previous Article  |  Next Article 

Journal of Virology, July 2000, p. 6418-6424, Vol. 74, No. 14
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes

James Arthos,1,* Andrea Rubbert,1,dagger Ronald L. Rabin,2 Claudia Cicala,1 Elizabeth Machado,1 Kathryne Wildt,1 Meredith Hanbach,1 Tavis D. Steenbeke,1 Ruth Swofford,2 Joshua M. Farber,2 and Anthony S. Fauci1

Laboratory of Immunoregulation1 and Laboratory of Clinical Investigation,2 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Received 28 December 1999/Accepted 14 April 2000

The capacity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelopes to transduce signals through chemokine coreceptors on macrophages was examined by measuring the ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to those observed when macrophages were treated with MIP-1beta . Distinct differences in the capacity of envelopes to mediate calcium mobilization were observed. Envelopes derived from viruses capable of replicating in macrophages mobilized relatively high levels of calcium, while envelopes derived from viruses incapable of replicating in macrophages mobilized relatively low levels of calcium. The failure to efficiently mobilize calcium was not restricted to envelopes derived from CXCR4-utilizing isolates but also included envelopes derived from CCR5-utilizing isolates that fail to replicate in macrophages. We characterized one CCR5-utilizing isolate, 92MW959, which entered macrophages but failed to replicate. A recombinant envelope derived from this virus mobilized low levels of calcium. When macrophages were inoculated with 92MW959 in the presence of MIP-1alpha , viral replication was observed, indicating that a CC chemokine-mediated signal provided the necessary stimulus to allow the virus to complete its replication cycle. Although the role that envelope-CCR5 signal transduction plays in viral replication is not yet understood, it has been suggested that envelope-mediated signals facilitate early postfusion events in viral replication. The data presented here are consistent with this hypothesis and suggest that the differential capacity of viral envelopes to signal through CCR5 may influence their ability to replicate in macrophages.

* Corresponding author. Mailing address: NIH, Bldg. 10, Rm. 6A-08, 10 Center Dr., Bethesda, MD 20892. Phone: (301) 402-3547. Fax: (301) 480-5244. E-mail: jarthos{at}nih.gov.

dagger Present address: Department of Clinical Medicine, University of Cologne, Cologne, Germany.

Journal of Virology, July 2000, p. 6418-6424, Vol. 74, No. 14
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Paruch, S., Heinis, M., Lemay, J., Hoeffel, G., Maranon, C., Hosmalin, A., Perianin, A. (2007). CCR5 signaling through phospholipase D involves p44/42 MAP-kinases and promotes HIV-1 LTR-directed gene expression. FASEB J. 21: 4038-4046 [Abstract] [Full Text]  
  • Melar, M., Ott, D. E., Hope, T. J. (2007). Physiological Levels of Virion-Associated Human Immunodeficiency Virus Type 1 Envelope Induce Coreceptor-Dependent Calcium Flux. J. Virol. 81: 1773-1785 [Abstract] [Full Text]  
  • Tomkowicz, B., Lee, C., Ravyn, V., Cheung, R., Ptasznik, A., Collman, R. G. (2006). The Src kinase Lyn is required for CCR5 signaling in response to MIP-1beta and R5 HIV-1 gp120 in human macrophages. Blood 108: 1145-1150 [Abstract] [Full Text]  
  • Kottilil, S., Shin, K., Jackson, J. O., Reitano, K. N., O'Shea, M. A., Yang, J., Hallahan, C. W., Lempicki, R., Arthos, J., Fauci, A. S. (2006). Innate Immune Dysfunction in HIV Infection: Effect of HIV Envelope-NK Cell Interactions. J. Immunol. 176: 1107-1114 [Abstract] [Full Text]  
  • Lin, Y.-L., Mettling, C., Portales, P., Reant, B., Clot, J., Corbeau, P. (2005). G-Protein Signaling Triggered by R5 Human Immunodeficiency Virus Type 1 Increases Virus Replication Efficiency in Primary T Lymphocytes. J. Virol. 79: 7938-7941 [Abstract] [Full Text]  
  • Yi, Y., Shaheen, F., Collman, R. G. (2005). Preferential Use of CXCR4 by R5X4 Human Immunodeficiency Virus Type 1 Isolates for Infection of Primary Lymphocytes. J. Virol. 79: 1480-1486 [Abstract] [Full Text]  
  • Balabanian, K., Harriague, J., Decrion, C., Lagane, B., Shorte, S., Baleux, F., Virelizier, J.-L., Arenzana-Seisdedos, F., Chakrabarti, L. A. (2004). CXCR4-Tropic HIV-1 Envelope Glycoprotein Functions as a Viral Chemokine in Unstimulated Primary CD4+ T Lymphocytes. J. Immunol. 173: 7150-7160 [Abstract] [Full Text]  
  • Lee, C., Liu, Q.-H., Tomkowicz, B., Yi, Y., Freedman, B. D., Collman, R. G. (2003). Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways. J. Leukoc. Biol. 74: 676-682 [Abstract] [Full Text]  
  • Arias, D. A., Navenot, J.-M., Zhang, W.-b., Broach, J., Peiper, S. C. (2003). Constitutive Activation of CCR5 and CCR2 Induced by Conformational Changes in the Conserved TXP Motif in Transmembrane Helix 2. J. Biol. Chem. 278: 36513-36521 [Abstract] [Full Text]  
  • Kinter, A. L., Umscheid, C. A., Arthos, J., Cicala, C., Lin, Y., Jackson, R., Donoghue, E., Ehler, L., Adelsberger, J., Rabin, R. L., Fauci, A. S. (2003). HIV Envelope Induces Virus Expression from Resting CD4+ T Cells Isolated from HIV-Infected Individuals in the Absence of Markers of Cellular Activation or Apoptosis. J. Immunol. 170: 2449-2455 [Abstract] [Full Text]  
  • Francois, F., Klotman, M. E. (2003). Phosphatidylinositol 3-Kinase Regulates Human Immunodeficiency Virus Type 1 Replication following Viral Entry in Primary CD4+ T Lymphocytes and Macrophages. J. Virol. 77: 2539-2549 [Abstract] [Full Text]  
  • Amara, A., Vidy, A., Boulla, G., Mollier, K., Garcia-Perez, J., Alcami, J., Blanpain, C., Parmentier, M., Virelizier, J.-L., Charneau, P., Arenzana-Seisdedos, F. (2003). G Protein-Dependent CCR5 Signaling Is Not Required for Efficient Infection of Primary T Lymphocytes and Macrophages by R5 Human Immunodeficiency Virus Type 1 Isolates. J. Virol. 77: 2550-2558 [Abstract] [Full Text]  
  • Pastore, C., Picchio, G. R., Galimi, F., Fish, R., Hartley, O., Offord, R. E., Mosier, D. E. (2003). Two Mechanisms for Human Immunodeficiency Virus Type 1 Inhibition by N-Terminal Modifications of RANTES. Antimicrob. Agents Chemother. 47: 509-517 [Abstract] [Full Text]  
  • Lin, Y.-L., Mettling, C., Portales, P., Reynes, J., Clot, J., Corbeau, P. (2002). Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection. Proc. Natl. Acad. Sci. USA 99: 15590-15595 [Abstract] [Full Text]  
  • Clapham, P. R., McKnight, A. (2002). Cell surface receptors, virus entry and tropism of primate lentiviruses. J. Gen. Virol. 83: 1809-1829 [Abstract] [Full Text]  
  • Cicala, C., Arthos, J., Selig, S. M., Dennis, G. Jr., Hosack, D. A., Van Ryk, D., Spangler, M. L., Steenbeke, T. D., Khazanie, P., Gupta, N., Yang, J., Daucher, M., Lempicki, R. A., Fauci, A. S. (2002). HIV envelope induces a cascade of cell signals in non-proliferating target cells that favor virus replication. Proc. Natl. Acad. Sci. USA 99: 9380-9385 [Abstract] [Full Text]  
  • Zhang, W.-b., Navenot, J.-M., Haribabu, B., Tamamura, H., Hiramatu, K., Omagari, A., Pei, G., Manfredi, J. P., Fujii, N., Broach, J. R., Peiper, S. C. (2002). A Point Mutation That Confers Constitutive Activity to CXCR4 Reveals That T140 Is an Inverse Agonist and That AMD3100 and ALX40-4C Are Weak Partial Agonists. J. Biol. Chem. 277: 24515-24521 [Abstract] [Full Text]  
  • Keppler, O. T., Welte, F. J., Ngo, T. A., Chin, P. S., Patton, K. S., Tsou, C.-L., Abbey, N. W., Sharkey, M. E., Grant, R. M., You, Y., Scarborough, J. D., Ellmeier, W., Littman, D. R., Stevenson, M., Charo, I. F., Herndier, B. G., Speck, R. F., Goldsmith, M. A. (2002). Progress Toward a Human CD4/CCR5 Transgenic Rat Model for De Novo Infection by Human Immunodeficiency Virus Type 1. JEM 195: 719-736 [Abstract] [Full Text]  
  • Choe, W., Volsky, D. J., Potash, M. J. (2001). Induction of Rapid and Extensive beta -Chemokine Synthesis in Macrophages by Human Immunodeficiency Virus Type 1 and gp120, Independently of Their Coreceptor Phenotype. J. Virol. 75: 10738-10745 [Abstract] [Full Text]  
  • Bannert, N., Farzan, M., Friend, D. S., Ochi, H., Price, K. S., Sodroski, J., Boyce, J. A. (2001). Human Mast Cell Progenitors Can Be Infected by Macrophagetropic Human Immunodeficiency Virus Type 1 and Retain Virus with Maturation In Vitro. J. Virol. 75: 10808-10814 [Abstract] [Full Text]  
  • Del Corno, M., Liu, Q.-H., Schols, D., de Clercq, E., Gessani, S., Freedman, B. D., Collman, R. G. (2001). HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin-insensitive chemokine receptor signaling. Blood 98: 2909-2916 [Abstract] [Full Text]  
  • Gorry, P. R., Bristol, G., Zack, J. A., Ritola, K., Swanstrom, R., Birch, C. J., Bell, J. E., Bannert, N., Crawford, K., Wang, H., Schols, D., De Clercq, E., Kunstman, K., Wolinsky, S. M., Gabuzda, D. (2001). Macrophage Tropism of Human Immunodeficiency Virus Type 1 Isolates from Brain and Lymphoid Tissues Predicts Neurotropism Independent of Coreceptor Specificity. J. Virol. 75: 10073-10089 [Abstract] [Full Text]  
  • Clayton, F., Kotler, D. P., Kuwada, S. K., Morgan, T., Stepan, C., Kuang, J., Le, J., Fantini, J. (2001). Gp120-Induced Bob/GPR15 Activation : A Possible Cause of Human Immunodeficiency Virus Enteropathy. Am. J. Pathol. 159: 1933-1939 [Abstract] [Full Text]  
  • Tokunaga, K., Greenberg, M. L., Morse, M. A., Cumming, R. I., Lyerly, H. K., Cullen, B. R. (2001). Molecular Basis for Cell Tropism of CXCR4-Dependent Human Immunodeficiency Virus Type 1 Isolates. J. Virol. 75: 6776-6785 [Abstract] [Full Text]  
  • Neil, S., Martin, F., Ikeda, Y., Collins, M. (2001). Postentry Restriction to Human Immunodeficiency Virus-Based Vector Transduction in Human Monocytes. J. Virol. 75: 5448-5456 [Abstract] [Full Text]  
  • Igarashi, T., Brown, C. R., Endo, Y., Buckler-White, A., Plishka, R., Bischofberger, N., Hirsch, V., Martin, M. A. (2000). Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans. Proc. Natl. Acad. Sci. USA 10.1073/pnas.021551798v1 [Abstract] [Full Text]  
  • Igarashi, T., Brown, C. R., Endo, Y., Buckler-White, A., Plishka, R., Bischofberger, N., Hirsch, V., Martin, M. A. (2001). Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans. Proc. Natl. Acad. Sci. USA 98: 658-663 [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»