Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells

Niederman, T. M. J.; Garcia, J. Victor; Hastings, William R.; Luria, S.; Ratner, Lee

doi:10.1128/jvi.66.10.6213-6219.1992

Cited by 113 publications

(41 citation statements)

References 34 publications

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“…It is also likely that HIV antigens tat, nef, gp120 or other HIV antigens may differentially regulate IL-10 in T cells and monocytes. HIV antigens tat and nef down-regulate the expression of several cellular genes including the cytokine genes [42][43][44]. The role of HIV antigens and/or cytokines in inhibiting IL-10 production by T cells at the transcriptional or post-transcriptional level remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

Kumar

Angel

Daftarian³

et al. 1998

Clinical and Experimental Immunology

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SUMMARYImmune unresponsiveness in HIV-1 infection can result from impaired signals delivered by the costimulatory CD28-B7 pathway and the altered production of immunoregulatory cytokines, in particular IL-10, whose production is altered in HIV-1 infection. In this study we investigate IL-10 regulation in T cells and monocytes from HIV þ individuals, and its association with CD28-mediated T cell proliferation. IL-10 production as analysed in T cell-and monocyte-depleted peripheral blood mononuclear cells (PBMC), and by intracellular staining at the single-cell level, reveals a defect in IL-10 production by CD4 þ and CD8 þ T cells, whereas monocytes constitute the major IL-10-producing cell type. To investigate the impact of IL-10 on immune responsiveness, CD28-mediated proliferative responses in HIV þ individuals were correlated with PHA-induced IL-10 production. CD4 þ T cells expressed CD28, yet exhibited markedly reduced CD28-mediated cell proliferation. This CD28-mediated CD4 þ T cell proliferation was found to be inversely associated with the levels of PHAinduced IL-10 production and could be restored, at least in part, by anti-IL-10 antibodies. These results suggest that IL-10 production is differentially regulated in T cells and monocytes of HIV þ individuals, and that IL-10 may have a role in inducing immune unresponsiveness by modulating the CD28-B7 pathway.

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Section: Discussionmentioning

confidence: 99%

Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

Kumar

Angel

Daftarian³

et al. 1998

Clinical and Experimental Immunology

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“…68 Contrasting with these results, several reports have suggested that Nef inhibits lymphocyte activation. 55,[69][70][71][72][73][74][75] This latter phenotype was observed for instance in Jurkat cell clones selected for the stable expression of HIV-1 nef or following the acute electroporation of recombinant, nonmyristoylated, Nef protein into human T lymphoid cells. 27 Supporters of the hyperactivation model see in this effect of Nef a way for the virus to create an environment favourable for its own gene expression and propagation.…”

Section: Nef and Signallingmentioning

confidence: 99%

The Nef protein of primate lentiviruses

Piguet¹,

Trono²

1999

Rev. Med. Virol.

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The Nef protein of primate lentiviruses acts as an important virulence factor in vivo both in monkeys and in humans. Among a human cohort of long‐term non‐progressors, several Nef defective HIV1 viruses have been isolated, indicating that Nef may accelerate HIV progression and disease in humans. Additionally, a Nef‐deleted SIV virus has low titres in rhesus monkeys and the animals develop AIDS at a much slower rate. In vitro, Nef can exert at least three kinds of effects: it downregulates CD4 and MHC class I, it stimulates virion infectivity and it alters signal transduction pathways. To accomplish this, Nef interacts with a series of cellular partners including CD4, components of the adaptor complexes AP‐1 and AP‐2, and several protein kinases, Nef often functioning as a connector between targets and effectors. The high degree of understanding of at least some aspects of Nef action, as well as the importance of this viral gene product for disease induction, identify Nef as a valuable target for the development of novel antiviral therapies. Moreover, the possibility of developing vaccines using attenuated viruses with deletions in nef and other crucial genes raises the possibility that the AIDS epidemic might one day be restrained. Copyright © 1999 John Wiley & Sons, Ltd.

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“…These effects of Nef include downregulation of CD4 [102][103][104][105][106] and blockage of TCR-mediated IL-2 production in Jurkat T cells [106,107]. The molecular basis of these effects is not entirely clear but may reflect the ability of Nef to inhibit the activation of NF-κB and/or AP-1 transcription factors [108][109][110] and to associate with cellular serine/threonine kinases [111][112][113][114][115][116][117].…”

Section: Interaction Of Pkcθ With the Hiv Protein Nefmentioning

confidence: 99%

New Perspectives on PKCθ, a Member of the Novel Subfamily of Protein Kinase C

1998

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Members of the protein kinase C (PKC) family of serine/threonine protein kinases have been implicated in numerous cellular responses in a large variety of cell types. Expression patterns of individual members and differences in their cofactor requirements and potential substrate specificity suggest that each isoenzyme may be involved in specific regulatory processes. The PKCtheta isoenzyme exhibits a relatively restricted expression pattern with high protein levels found predominantly in hematopoietic cells and skeletal muscle. PKCtheta was found to be expressed in T, but not B lymphocytes, and to colocalize with the T-cell antigen receptor (TCR) at the site of contact between the antigen-responding T cell and the antigen-presenting cell (APC). Colocalization of PKCtheta with the TCR was selective for this isoenzyme and occurred only upon antigen-mediated responses leading to T-cell activation and proliferation. PKCtheta was found to be involved in the regulation of transcriptional activation of early-activation genes, predominantly AP-1, and its cellular distribution and activation were found to be regulated by the 14-3-3 protein. Other findings indicated that PKCtheta can associate with the HIV negative factor (Nef) protein, suggesting that altered regulation of PKCtheta by Nef may contribute to the T-cell impairments that are characteristic of infection by HIV. PKCtheta is expressed at relatively high levels in skeletal muscle, where it is suggested to play a role in signal transduction in both the developing and mature neuromuscular junction. In addition, PKCtheta appears to be involved in the insulin-mediated response of intact skeletal muscle, as well as in experimentally induced insulin resistance of skeletal muscle. Further studies suggest that PKCtheta is expressed in endothelial cells and is involved in multiple processes essential for angiogenesis and wound healing, including the regulation of cell cycle progression, formation and maintenance of actin cytoskeleton, and formation of capillary tubes. Here, we review recent progress in the study of PKCtheta and discuss its potential role in various cellular responses.

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Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells

Cited by 113 publications

References 34 publications

Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

Differential production of IL-10 by T cells and monocytes of HIV-infected individuals: association of IL-10 production with CD28-mediated immune responsiveness

The Nef protein of primate lentiviruses

New Perspectives on PKCθ, a Member of the Novel Subfamily of Protein Kinase C

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