NF-κ B-Dependent and -Independent Pathways of HIV Activation in a Chronically Infected T Cell Line

Antoni, Beth Ann; Rabson, Arnold B.; Kinter, Audrey; Bodkin, Marlon; Poli, Guido

doi:10.1006/viro.1994.1390

Cited by 64 publications

(52 citation statements)

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“…PTX-B significantly reduced the level of MS and US viral RNAs induced by TNF-␣, along with suppressive effects on viral protein expression and output of the virion progeny as measured by RT activity in culture supernatants. In this regard, it is well established that TNF-␣-mediated effects are mostly dependent upon the activation of the cellular transcription factor NF-B (36,37,53,54). Quite surprisingly, PTX-B did not perturb the ability of TNF-␣ to activate NF-B in U1 cells both early (30 min) and up to 4 h after cytokine stimulation, although it inhibited the basal LTR-mediated transcription in both U1 and U937 promonocytic cells.…”

Section: Discussionmentioning

confidence: 91%

“…TNF-␣ is a classic transcriptional inducer of viral expression mainly operating via activation of the cellular transcription factor NF-B (35,36,53,54). In this regard, it has been independently reported that PTX, but not PTX-B, blocked TNF-␣-induced HIV-1 expression in U1 cells through inactivation of G i protein (55).…”

Section: Ptx-b Inhibits Tnf-␣-dependent Expression Of Hiv Independentmentioning

confidence: 99%

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The Binding Subunit of Pertussis Toxin Inhibits HIV Replication in Human Macrophages and Virus Expression in Chronically Infected Promonocytic U1 Cells

Alfano¹,

Vallanti²,

Biswas³

et al. 2001

The Journal of Immunology

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We have recently shown that the binding subunit of pertussis toxin (PTX-B) inhibits the entry and replication of macrophage-tropic (R5) HIV-1 strains in activated primary T lymphocytes. Furthermore, PTX-B suppressed the replication of T cell-tropic (X4) viruses at a postentry level in the same cells. In this study we demonstrate that PTX-B profoundly impairs entry and replication of the HIV-1ADA (R5), as well as of HIV pseudotyped with either murine leukemia virus or vesicular stomatitis virus envelopes, in primary monocyte-derived macrophages. In addition, PTX-B strongly inhibited X4 HIV-1 replication in U937 promonocytic cells and virus expression in the U937-derived chronically infected U1 cell line stimulated with cytokines such as TNF-α and IL-6. Of interest, TNF-α-mediated activation of the cellular transcription factor NF-κB was unaffected by PTX-B. Therefore, PTX-B may represent a novel and potent inhibitor of HIV-1 replication to be tested for efficacy in infected individuals. In support of this proposition, a genetically modified mutant of PTX (PT-9K/129G), which is safely administered for prevention of Bordetella pertussis infection, showed an in vitro anti-HIV profile superimposable to that of PTX-B.

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Section: Discussionmentioning

confidence: 91%

Section: Ptx-b Inhibits Tnf-␣-dependent Expression Of Hiv Independentmentioning

confidence: 99%

The Binding Subunit of Pertussis Toxin Inhibits HIV Replication in Human Macrophages and Virus Expression in Chronically Infected Promonocytic U1 Cells

Alfano¹,

Vallanti²,

Biswas³

et al. 2001

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

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“…Glycerol Gradients-Glycerol gradients (10 -30%) were established by pipetting 2 ml of each glycerol fraction (10,15,20,25, and 30%, v/v) in medium-salt buffer A into centrifugation tubes (Beckman 331372). Gradients were formed by standing for 6 h at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Bromodomain and Extra-terminal (BET) Bromodomain Inhibition Activate Transcription via Transient Release of Positive Transcription Elongation Factor b (P-TEFb) from 7SK Small Nuclear Ribonucleoprotein

Bartholomeeusen

Xiang

Fujinaga

et al. 2012

Journal of Biological Chemistry

180

162

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Background: P-TEFb regulates transcription elongation, cell growth, and proliferation. Results: BET bromodomain inhibition by JQ1 transiently releases free P-TEFb from the inactive 7SK snRNP, thus activating HEXIM1 and HIV transcription. Conclusion: JQ1 affects the P-TEFb equilibrium. Significance: P-TEFb release from and reassembly into 7SK snRNP by JQ1 inhibits tumor cell growth and reactivates latent HIV.

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“…the ACH2 cell line (34) and the U1 promonocytic cell line (36)) or in the 5Ј-LTR (e.g. the J⌬K cell line (35)). The J89GFP cells were maintained in RMPI 1640 medium supplemented with 10% FBS, 0.3 mg/ml L-glutamine, 100 units/ml penicillin, and 100 g/ml streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Inhibitors of Histone Deacetylases

Huber¹,

Doyon²,

Plaks

et al. 2011

Journal of Biological Chemistry

130

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Deacetylation of histone proteins at the HIV type 1 (HIV-1) long terminal repeat (LTR) by histone deactylases (HDACs) can promote transcriptional repression and virus latency. As such, HDAC inhibitors (HDACI) could be used to deplete reservoirs of persistent, quiescent HIV-1 proviral infection. However, the development of HDACI to purge latent HIV-1 requires knowledge of the HDAC isoforms contributing to viral latency and the development of inhibitors specific to these isoforms. In this study, we identify the HDACs responsible for HIV-1 latency in Jurkat J89GFP cells using a chemical approach that correlates HDACI isoform specificity with their ability to reactivate latent HIV-1 expression. We demonstrate that potent inhibition or knockdown of HDAC1, an HDAC isoform reported to drive HIV-1 into latency, was not sufficient to de-repress the viral LTR. Instead, we found that inhibition of HDAC3 was necessary to activate latent HIV-1. Consistent with this finding, we identified HDAC3 at the HIV-1 LTR by chromatin immunoprecipitation. Interestingly, we show that valproic acid is a weak inhibitor of HDAC3 (IC 50 ‫؍‬ 5.5 mM) relative to HDAC1 (IC 50 ‫؍‬ 170 M). Because the total therapeutic concentration of valproic acid ranges from 275 to 700 M in adults, these data may explain why this inhibitor has no effect on the decay of latent HIV reservoirs in patients. Taken together, our study suggests an important role for HDAC3 in HIV-1 latency and, importantly, describes a chemical approach that can readily be used to identify the HDAC isoforms that contribute to HIV-1 latency in other cell types.

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NF-κ B-Dependent and -Independent Pathways of HIV Activation in a Chronically Infected T Cell Line

Cited by 64 publications

References 0 publications

The Binding Subunit of Pertussis Toxin Inhibits HIV Replication in Human Macrophages and Virus Expression in Chronically Infected Promonocytic U1 Cells

The Binding Subunit of Pertussis Toxin Inhibits HIV Replication in Human Macrophages and Virus Expression in Chronically Infected Promonocytic U1 Cells

Bromodomain and Extra-terminal (BET) Bromodomain Inhibition Activate Transcription via Transient Release of Positive Transcription Elongation Factor b (P-TEFb) from 7SK Small Nuclear Ribonucleoprotein

Inhibitors of Histone Deacetylases

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