The T Cell Activation Factor NF-ATc Positively Regulates HIV-1 Replication and Gene Expression in T Cells

Kinoshita, Shigemi; Su, Lishan; Amano, Masahiko; Timmerman, Luika; Kaneshima, Hideto; Nolan, Garry P.

doi:10.1016/s1074-7613(00)80326-x

Cited by 288 publications

(297 citation statements)

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“…Similar overlapping binding sequences from the NF-‹ B/ NF-AT families of transcription factors have also been found in several cytokine genes [31] and in the transcriptional enhancers of HIV-1 and HIV-2 [32]. NF-AT family members have been shown to productively bind the ‹ B regulatory elements and synergize with NF-‹ B in transcriptional activation of HIV-1 in T cells [32].…”

Section: Discussionmentioning

confidence: 61%

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NF‐κB synergizes with NF‐AT and NF‐IL6 in activation of the IL‐4 gene in T cells

et al. 2004

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IL‐4 plays a pivotal role in the development of the Th2 cell mediated humoral immune response and causes IgE‐dependent allergic inflammatory diseases. Expression of IL‐4 in differentiated Th2 cells is regulated by transcription factors such as NF‐AT, AP‐1 and NF‐IL6. Recently, increasing evidence indicates that the pro‐inflammatory transcription factor NF‐κB may also participate inIL‐4 expression. In this study, we show that the IL‐4 promoter is synergistically activated by NF‐κB, NF‐AT and NF‐IL6 at the NF‐κB/NF‐AT/NF‐IL6 composite sites. In addition, we performed the chromatin immunoprecipitation technique to determine the functional relevance of NF‐κB in the activation of the IL‐4 gene in vivo. We demonstrate that NF‐κB binds to the IL‐4 promoter in vivo upon T cell activation. Inhibition of NF‐κB nuclear translocation in living cells blocked binding of NF‐κB to the IL‐4 promoter. The data provide first evidence that NF‐κB is directly involved in IL‐4 transcription.

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Section: Discussionmentioning

confidence: 61%

“…NF-AT family members have been shown to productively bind the ‹ B regulatory elements and synergize with NF-‹ B in transcriptional activation of HIV-1 in T cells [32]. This indicates that this pattern of nuclear protein-binding sites might reflect an evolutionarily conserved mechanism for regulating inducible expression of T cell genes.…”

Section: Discussionmentioning

confidence: 97%

NF‐κB synergizes with NF‐AT and NF‐IL6 in activation of the IL‐4 gene in T cells

et al. 2004

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“…Up to now, however, these findings have been explained by an interplay of viral and host regulatory proteins, such as Tat, Rev, Nef, NF-B, and NF-AT. The interaction between these viral and cellular proteins leads to increased HIV long terminal repeat-driven transcription and viral replication (78,79). We propose that T cell activation may influence HIV infection in two ways.…”

Section: Discussionmentioning

confidence: 97%

Glucocorticoids Regulate TCR-Induced Elevation of CD4: Functional Implications

Wiegers

Stec

Klinkert

et al. 2000

The Journal of Immunology

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CD4 serves as a coreceptor during Ag recognition by the TCR. This interaction results in a marked increase in the sensitivity of a T cell to Ag presented by MHC class II molecules. Here we report that activation of T cells either by plate-bound mAb (anti-TCR, anti-CD3) or soluble activators (staphylococcal enterotoxin A, Con A) is associated with an (up to 3-fold) increase in CD4 cell surface expression on CD25+ cells, which was maximal after 72–96 h. Incubation with the glucocorticoid hormone corticosterone (CORT) shifted the enhancement of CD4 expression to a point about 24 h earlier than that observed in control cultures. In parallel, the proliferative response of these CORT-treated cells was profoundly enhanced. An involvement of increased CD4 expression in this enhanced proliferative response was evidenced by the observation that T cell proliferation in CORT-treated cultures was much less sensitive to inhibition by an inhibitory, nondepleting anti-CD4 mAb than that in control cultures. TCR down-regulation was, however, not affected by CORT. Thus, based on this study and previous reports we propose that both TCR-mediated signals and glucocorticoids are important physiological regulators of CD4 expression. In addition, these findings may be of significance for the sensitivity of CD4+ cells to HIV infection upon T cell activation, as the efficacy of primary patient HIV entry depends on the level of surface CD4.

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“…For example, T cell activation is required for efficient HIV-1 replication in resting T cells (30,31). Activation of transcription factors such as NF-B (32) and NF-ATc (33,34) leads to enhanced HIV gene expression and replication. Although the Rho GTPases have been implicated in T cell activation (23,28,35), little is known about how Rho GTPases affect HIV-1 replication.…”

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confidence: 99%

Modulation of HIV-1 Replication by a Novel RhoA Effector Activity

Wang

Zhang

Solski

et al. 2000

The Journal of Immunology

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The RhoA GTPase is involved in regulating actin cytoskeletal organization, gene expression, cell proliferation, and survival. We report here that p115-RhoGEF, a specific guanine nucleotide exchange factor (GEF) and activator of RhoA, modulates HIV-1 replication. Ectopic expression of p115-RhoGEF or Gα13, which activates p115-RhoGEF activity, leads to inhibition of HIV-1 replication. RhoA activation is required and the inhibition affects HIV-1 gene expression. The RhoA effector activity in inhibiting HIV-1 replication is genetically separable from its activities in transformation of NIH3T3 cells, activation of serum response factor, and actin stress fiber formation. These findings reveal that the RhoA signal transduction pathway regulates HIV-1 replication and suggest that RhoA inhibits HIV-1 replication via a novel effector activity.

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The T Cell Activation Factor NF-ATc Positively Regulates HIV-1 Replication and Gene Expression in T Cells

Abstract: al., 1990). Therefore it has been long suggested that NF-Stanford University School of Medicine B, which binds to these elements, is a critical transcrip-Stanford California 94305 tion factor for HIV-1 gene regulation in T cells (Nabel Systemix, Inc. and Baltimore, 1987).

Cited by 288 publications

References 56 publications

NF‐κB synergizes with NF‐AT and NF‐IL6 in activation of the IL‐4 gene in T cells

NF‐κB synergizes with NF‐AT and NF‐IL6 in activation of the IL‐4 gene in T cells

Glucocorticoids Regulate TCR-Induced Elevation of CD4: Functional Implications

Modulation of HIV-1 Replication by a Novel RhoA Effector Activity

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