| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Immunology,
Department of Ultrastructures, Istituto Superiore di Sanità, 00161 Rome, Italy
1Correspondence: Department of Immunology, Istituto Superiore di Sanità Viale Regina Elena, 299 00161 Rome, Italy. E-mail: viora{at}iss.it
The accessory HIV-1 Nef protein plays a key role in AIDS pathogenesis. We recently demonstrated that exogenous Nef triggers phenotypic and functional differentiation of immature dendritic cells (DCs). Here we investigated whether the Nef-induced DC differentiation occurs with morphological remodeling and have focused on the interference of Nef in the signaling pathways that regulates DC maturation. We found that exogenous Nef enters immature DCs, promoting their functional and morphological differentiation. Specifically, Nef promotes interleukin (IL) -12 release, which closely fits with nuclear factor (NF) -
B activation. Nef induces rearrangement of actin microfilaments, leading to uropod and ruffle formation. Moreover, Nef increases the capacity of DCs to form clusters with allogeneic CD4+ T cells, improving immunological synapse formation. Searching for molecules involved in Nef-triggered signaling pathways driving the DC maturation, we found that Nef targets Vav and promotes its tyrosine phosphorylation, associated with its nucleus-to-cytoplasm redistribution. This has a direct effect on Vav guanine nucleotide exchange factor activity for the small GTPase Rac1. We hypothesize that targeting Vav, Nef modulates both early signaling events (such as cytoskeletal rearrangement) and delayed responses (such as transcriptional regulation), promoting DC differentiation. Our results highlight how Nef may enhance T lymphocyte activation, thus fostering virus dissemination, manipulating the DC arm of the immune response.—Quaranta, M. G., Mattioli, B., Spadaro, F., Straface, E., Giordani, L., Ramoni, C., Malorni, W., Viora, M. HIV-1 Nef triggers Vav-mediated signaling pathway leading to functional and morphological differentiation of dendritic cells.
Key Words: AIDS immunopathogenesis • exogenous Nef • signal transduction • cytoskeleton rearrangement
This article has been cited by other articles:
|
|
 |
|
  B. Mattioli, E. Straface, P. Matarrese, M. G. Quaranta, L. Giordani, W. Malorni, and M. Viora Leptin as an immunological adjuvant: enhanced migratory and CD8+ T cell stimulatory capacity of human dendritic cells exposed to leptin FASEB J, June 1, 2008; 22(6): 2012 - 2022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-c. Lu, J. C. He, Z.-h. Wang, X. Feng, T. Fukumi-Tominaga, N. Chen, J. Xu, R. Iyengar, and P. E. Klotman HIV-1 Nef Disrupts the Podocyte Actin Cytoskeleton by Interacting with Diaphanous Interacting Protein J. Biol. Chem., March 28, 2008; 283(13): 8173 - 8182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rauch, K. Pulkkinen, K. Saksela, and O. T. Fackler Human Immunodeficiency Virus Type 1 Nef Recruits the Guanine Exchange Factor Vav1 via an Unexpected Interface into Plasma Membrane Microdomains for Association with p21-Activated Kinase 2 Activity J. Virol., March 15, 2008; 82(6): 2918 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hoffmann, J. Seebach, A. Cosma, F. D. Goebel, K. Strimmer, H. M. Schatzl, and V. Erfle Therapeutic vaccination reduces HIV sequence variability FASEB J, February 1, 2008; 22(2): 437 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Quaranta, A. Napolitano, M. Sanchez, L. Giordani, B. Mattioli, and M. Viora HIV-1 Nef impairs the dynamic of DC/NK crosstalk: different outcome of CD56dim and CD56bright NK cell subsets FASEB J, August 1, 2007; 21(10): 2323 - 2334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Majumder, N. J. Venkatachari, E. A. Schafer, M. L. Janket, and V. Ayyavoo Dendritic Cells Infected with vpr-Positive Human Immunodeficiency Virus Type 1 Induce CD8+ T-Cell Apoptosis via Upregulation of Tumor Necrosis Factor Alpha J. Virol., July 15, 2007; 81(14): 7388 - 7399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Mangino, Z. A. Percario, G. Fiorucci, G. Vaccari, S. Manrique, G. Romeo, M. Federico, M. Geyer, and E. Affabris In Vitro Treatment of Human Monocytes/Macrophages with Myristoylated Recombinant Nef of Human Immunodeficiency Virus Type 1 Leads to the Activation of Mitogen-Activated Protein Kinases, I{kappa}B Kinases, and Interferon Regulatory Factor 3 and to the Release of Beta Interferon J. Virol., March 15, 2007; 81(6): 2777 - 2791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Quaranta, B. Mattioli, L. Giordani, and M. Viora The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS FASEB J, November 1, 2006; 20(13): 2198 - 2208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Haller, S. Rauch, N. Michel, S. Hannemann, M. J. Lehmann, O. T. Keppler, and O. T. Fackler The HIV-1 Pathogenicity Factor Nef Interferes with Maturation of Stimulatory T-lymphocyte Contacts by Modulation of N-Wasp Activity J. Biol. Chem., July 14, 2006; 281(28): 19618 - 19630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mann, C. N. Patrick, M. S. Cragg, J. Honeychurch, D. A. Mann, and M. Harris Functional Analysis of HIV Type 1 Nef Reveals a Role for PAK2 as a Regulator of Cell Phenotype and Function in the Murine Dendritic Cell Line, DC2.4 J. Immunol., November 15, 2005; 175(10): 6560 - 6569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Khan, L. Jin, L. Miles, V. C. Bond, and M. D. Powell Chimeric Human Immunodeficiency Virus Type 1 Virions That Contain the Simian Immunodeficiency Virus nef Gene Are Cyclosporin A Resistant J. Virol., March 1, 2005; 79(5): 3211 - 3216. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
