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 Meier, A.
Right arrow Articles by Altfeld, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meier, A.
Right arrow Articles by Altfeld, M.

 Previous Article  |  Next Article 

Journal of Virology, August 2007, p. 8180-8191, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00421-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

MyD88-Dependent Immune Activation Mediated by Human Immunodeficiency Virus Type 1-Encoded Toll-Like Receptor Ligands{triangledown}

Angela Meier,1,# Galit Alter,1,# Nicole Frahm,1,2 Harlyn Sidhu,1 Bin Li,1 Aranya Bagchi,2 Nickolas Teigen,1 Hendrik Streeck,1 Hans-Juergen Stellbrink,3 Judith Hellman,2 Jan van Lunzen,4 and Marcus Altfeld1*

Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts,1 Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts,2 IPM Study Center, Hamburg, Germany,3 University Medical Center Hamburg-Eppendorf, Infectious Disease Unit, Hamburg, Germany4

Received 27 February 2007/ Accepted 7 May 2007

Immune activation is a major characteristic of human immunodeficiency virus type 1 (HIV-1) infection and a strong prognostic factor for HIV-1 disease progression. The underlying mechanisms leading to immune activation in viremic HIV-1 infection, however, are not fully understood. Here we show that, following the initiation of highly active antiretroviral therapy, the immediate decline of immune activation is closely associated with the reduction of HIV-1 viremia, which suggests a direct contribution of HIV-1 itself to immune activation. To propose a mechanism, we demonstrate that the single-stranded RNA of HIV-1 encodes multiple uridine-rich Toll-like receptor 7/8 (TLR7/8) ligands that induce strong MyD88-dependent plasmacytoid dendritic cell and monocyte activation, as well as accessory cell-dependent T-cell activation. HIV-1-encoded TLR ligands may, therefore, directly contribute to the immune activation observed during viremic HIV-1 infection. These data provide an initial rationale for inhibiting the TLR pathway to directly reduce the chronic immune activation induced by HIV-1 and the associated immune pathogenesis.

* Corresponding author. Mailing address: Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129. Phone: (617) 724-2461. Fax: (617) 724-8586. E-mail: maltfeld{at}partners.org

{triangledown} Published ahead of print on 16 May 2007.

# A.M. and G.A. contributed equally to this work.

Journal of Virology, August 2007, p. 8180-8191, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00421-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Burgers, W. A., Riou, C., Mlotshwa, M., Maenetje, P., de Assis Rosa, D., Brenchley, J., Mlisana, K., Douek, D. C., Koup, R., Roederer, M., de Bruyn, G., Karim, S. A., Williamson, C., Gray, C. M., and the CAPRISA 002 Acute Infection Study Team, (2009). Association of HIV-Specific and Total CD8+ T Memory Phenotypes in Subtype C HIV-1 Infection with Viral Set Point. J. Immunol. 182: 4751-4761 [Abstract] [Full Text]  
  • Szczepanski, M. J., Czystowska, M., Szajnik, M., Harasymczuk, M., Boyiadzis, M., Kruk-Zagajewska, A., Szyfter, W., Zeromski, J., Whiteside, T. L. (2009). Triggering of Toll-like Receptor 4 Expressed on Human Head and Neck Squamous Cell Carcinoma Promotes Tumor Development and Protects the Tumor from Immune Attack. Cancer Res. 69: 3105-3113 [Abstract] [Full Text]  
  • Gargano, L. M., Forrest, J. C., Speck, S. H. (2009). Signaling through Toll-Like Receptors Induces Murine Gammaherpesvirus 68 Reactivation In Vivo. J. Virol. 83: 1474-1482 [Abstract] [Full Text]  
  • Chang, J. J., Altfeld, M. (2009). TLR-mediated immune activation in HIV. Blood 113: 269-270 [Full Text]  
  • Baenziger, S., Heikenwalder, M., Johansen, P., Schlaepfer, E., Hofer, U., Miller, R. C., Diemand, S., Honda, K., Kundig, T. M., Aguzzi, A., Speck, R. F. (2009). Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology. Blood 113: 377-388 [Abstract] [Full Text]  
  • Smits, E. L. J. M., Ponsaerts, P., Berneman, Z. N., Van Tendeloo, V. F. I. (2008). The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy. The Oncologist 13: 859-875 [Abstract] [Full Text]  
  • Tilton, J. C., Manion, M. M., Luskin, M. R., Johnson, A. J., Patamawenu, A. A., Hallahan, C. W., Cogliano-Shutta, N. A., Mican, J. M., Davey, R. T. Jr., Kottilil, S., Lifson, J. D., Metcalf, J. A., Lempicki, R. A., Connors, M. (2008). Human Immunodeficiency Virus Viremia Induces Plasmacytoid Dendritic Cell Activation In Vivo and Diminished Alpha Interferon Production In Vitro. J. Virol. 82: 3997-4006 [Abstract] [Full Text]  
  • Lee, A. W., Sharp, E. R., O'Mahony, A., Rosenberg, M. G., Israelski, D. M., Nolan, G. P., Nixon, D. F. (2008). Single-Cell, Phosphoepitope-Specific Analysis Demonstrates Cell Type- and Pathway-Specific Dysregulation of Jak/STAT and MAPK Signaling Associated with In Vivo Human Immunodeficiency Virus Type 1 Infection. J. Virol. 82: 3702-3712 [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»