| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Infectious Diseases and Hospital Epidemiology, Department of Internal Medicine and
Institute of Clinical Immunology, University Hospital of Zurich, Zurich, Switzerland
TLRs trigger innate immunity by recognizing conserved motifs of microorganisms. Recently, ssRNAs from HIV and influenza virus were shown to trigger TLR7 and 8. Thus, we hypothesized that HIV ssRNA, by triggering TLR7/8, affects HIV pathogenesis. Indeed, HIV ssRNA rendered human lymphoid tissue of tonsillar origin or PBMC barely permissive to HIV replication. The synthetic compound R-848, which also triggers TLR7/8, showed similar anti-HIV activity. Loss of R-848’s activity in lymphoid tissue depleted of B cells suggested a role for B cells in innate immunity. TLR7/8 triggering appears to exert antiviral effects through soluble factors: conditioned medium reduced HIV replication in indicator cells. Although a number of cytokines and chemokines were increased upon adding R-848 to lymphoid tissue, blocking those cytokines/chemokines (i.e., IFN-
receptor, IFN-
, MIP-1, -1
, RANTES, and stromal cell-derived factor-1) did not result in the reversal of R-848’s anti-HIV activity. Thus, the nature of this soluble factor(s) remains unknown. Unlike lymphoid tissue acutely infected with HIV, triggering latently infected promonocytic cells induced the release of HIV virions. The anti-HIV effects of triggering TLR7/8 may inhibit rapid killing, while pro-HIV effects may guarantee a certain replication level. Compounds triggering TLR7/8 may be attractive drug candidates to purge latent HIV while preventing new infections.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  S. Geuenich, L. Kaderali, I. Allespach, S. Sertel, and O. T. Keppler Biological Signature Characteristics of Primary Isolates from Human Immunodeficiency Virus Type 1 Group O in Ex Vivo Human Tonsil Histocultures J. Virol., October 15, 2009; 83(20): 10494 - 10503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Vanden Bush, C. M. Buchta, J. Claudio, and G. A. Bishop Cutting Edge: Importance of IL-6 and Cooperation between Innate and Adaptive Immune Receptors in Cellular Vaccination with B Lymphocytes J. Immunol., October 15, 2009; 183(8): 4833 - 4837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Poovassery, T. J. Vanden Bush, and G. A. Bishop Antigen Receptor Signals Rescue B Cells from TLR Tolerance J. Immunol., September 1, 2009; 183(5): 2974 - 2983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, A. J. Smith, T. W. Schacker, J. V. Carlis, L. Duan, C. S. Reilly, and A. T. Haase Microarray Analysis of Lymphatic Tissue Reveals Stage-Specific, Gene Expression Signatures in HIV-1 Infection J. Immunol., August 1, 2009; 183(3): 1975 - 1982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Trapp, N. R. Derby, R. Singer, A. Shaw, V. G. Williams, S. G. Turville, J. W. Bess Jr., J. D. Lifson, and M. Robbiani Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G J. Virol., January 15, 2009; 83(2): 884 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Baenziger, M. Heikenwalder, P. Johansen, E. Schlaepfer, U. Hofer, R. C. Miller, S. Diemand, K. Honda, T. M. Kundig, A. Aguzzi, et al. Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology Blood, January 8, 2009; 113(2): 377 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Doyle, C. A. Jefferies, C. Feighery, and L. A. J. O'Neill Signaling by Toll-like Receptors 8 and 9 Requires Bruton's Tyrosine Kinase J. Biol. Chem., December 21, 2007; 282(51): 36953 - 36960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Marshall, D. S. Heeke, M. L. Gesner, B. Livingston, and G. Van Nest Negative regulation of TLR9-mediated IFN-{alpha} induction by a small-molecule, synthetic TLR7 ligand J. Leukoc. Biol., September 1, 2007; 82(3): 497 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hattermann, S. Picard, M. Borgeat, P. Leclerc, M. Pouliot, and P. Borgeat The Toll-like receptor 7/8-ligand resiquimod (R-848) primes human neutrophils for leukotriene B4, prostaglandin E2 and platelet-activating factor biosynthesis FASEB J, May 1, 2007; 21(7): 1575 - 1585. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
