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Possati, L; Campioni, Diana; Sola, Francesco; Leone, L.; Ferrante, Luigi; Trabanelli, Cecilia; Ciomei, Marina; Montesi, Michela; Rocchetti, Romina; Talevi, Simona; Bompadre, Stefano; Caputo, Antonella; Barbanti‐Brodano, Giuseppe; Corallini, Alfredo

doi:10.1023/a:1006737029616

Cited by 14 publications

(3 citation statements)

References 31 publications

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“…Previous data obtained in, in vitro and in vivo models of KS and angiogenesis indicated that anti-Tat Abs can neutralize the activity of extracellular Tat [24,46,60]. The results described here, confirm and extend those studies by using an in vivo model of Tat-induced, IC-promoted KS-like lesions that more closely resemble the microenvironment leading to AIDS-KS.…”

Section: Discussionsupporting

confidence: 88%

Kaposi’s Sarcoma Lesion Progression in BKV-Tat Transgenic Mice Is Increased by Inflammatory Cytokines and Blocked by Treatment with Anti-Tat Antibodies

Brocca-Cofano

Sgadari

Picconi

et al. 2022

IJMS

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Kaposi’s sarcoma (KS) is an angioproliferative tumor showing an increased frequency and aggressiveness in HIV-infected subjects (AIDS-KS), due to the combined effects of inflammatory cytokines (IC), angiogenic factors, and the HIV-1 Tat protein. While the introduction of effective combined antiretroviral regimens greatly improved AIDS-KS incidence and course, it continues to be an incurable disease and the development of new rational targeted therapies is warranted. We used the BKV/Tat transgenic mouse model to evaluate the effects of IC and anti-Tat antibodies (Abs) treatment on KS-like lesions arising in BKV/Tat mice. We demonstrated here that IC-treatment increases the severity and delays the regression of KS-like lesions. Further, anti-Tat Abs reduced KS-like lesion severity developing in IC-treated mice when anti-Tat Abs were administered at an early-stage of lesion development as compared to more advanced lesions. Early anti-Tat Abs treatment also accelerated KS-like lesion regression and reduced the rate of severe-grade lesions. This effect was more evident in the first weeks after Ab treatment, suggesting that a longer treatment with anti-Tat Abs might be even more effective, particularly if administered just after lesion development. Although preliminary, these results are encouraging, and the approach deserves further studies for the development of anti-Tat Ab-based therapies for AIDS-KS. Clinical studies specifically addressing the effect of anti-Tat antibodies in treating AIDS-KS are not yet available. Nevertheless, the effectiveness of anti-Tat antibodies in controlling HIV/AIDS progression, likely due to the neutralization of extracellular Tat activities, is suggested by several cross-sectional and longitudinal clinical studies, indicating that anti-Tat Ab treatment or Tat-based vaccines may be effective to treat AIDS-KS patients or prevent the tumor in individuals at risk.

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Section: Discussionsupporting

confidence: 88%

Kaposi’s Sarcoma Lesion Progression in BKV-Tat Transgenic Mice Is Increased by Inflammatory Cytokines and Blocked by Treatment with Anti-Tat Antibodies

Brocca-Cofano

Sgadari

Picconi

et al. 2022

IJMS

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“…Some of these compounds, including unmodified heparin, heparan sulfate, and suramin-like distamycin A derivatives, although not dextran sulfate, ␤-cyclodextrin, chemically desulfated or low molecular weight heparins, also bind extracellular Tat and inhibit its biological activity in vitro (9,10,14,17) and in vivo (18). Thus, selected polyanionic molecules endowed with the capacity to affect HIV life cycle at different levels can be exploited for the development of novel "multitarget" anti-AIDS drugs.…”

mentioning

confidence: 99%

Pentosan Polysulfate as an Inhibitor of Extracellular HIV-1 Tat

Rusnati¹,

Urbinati²,

Caputo³

et al. 2001

Journal of Biological Chemistry

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“…For instance, polysulfonated distamycin A derivatives (PNU145156E and PNU153429) were found to interact and sequester extracellular Tat in the extracellular space as well as to inhibit intracellular Tat when these compounds were introduced by lipofection into the cells (Corallini et al 1998). These compounds blocked Tat-induced neoangiogenesis in T53c14 cells (Corallini et al 1998) and delay Tat-induced tumor growth and neovascularization in Kaposi’s sarcoma-like tumor model (Possati et al 1999). …”

Section: Inhibition Of Extracellular Tatmentioning

confidence: 99%

Targeting HIV Transcription: The Quest for a Functional Cure

Mousseau

Mediouni

Valente

2015

The Future of HIV-1 Therapeutics

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Antiretroviral therapy (ART) potently suppresses HIV-1 replication, but the virus persists in quiescent infected CD4+T cells as a latent integrated provirus, and patients must indefinitely remain on therapy. If ART is terminated, these integrated proviruses can reactivate, driving new rounds of infection. A functional cure for HIV requires eliminating low-level ongoing viral replication that persists in certain tissue sanctuaries and preventing viral reactivation. The HIV Tat protein plays an essential role in HIV transcription by recruiting the kinase activity of the P-TEFb complex to the viral mRNA’s stem–bulge–loop structure, TAR, activating transcriptional elongation. Because the Tat-mediated transactivation cascade is critical for robust HIV replication, the Tat/TAR/P-TEFb complex is one of the most attractive targets for drug development. Importantly, compounds that interfere with transcription could impair viral reactivation, low-level ongoing replication, and replenishment of the latent reservoir, thereby reducing the size of the latent reservoir pool. Here, we discuss the potential importance of transcriptional inhibitors in the treatment of latent HIV-1 disease and review recent findings on targeting Tat, TAR, and P-TEFb individually or as part of a complex. Finally, we discuss the impact of extracellular Tat in HIV-associated neurocognitive disorders and cancers.

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Untitled

Cited by 14 publications

References 31 publications

Kaposi’s Sarcoma Lesion Progression in BKV-Tat Transgenic Mice Is Increased by Inflammatory Cytokines and Blocked by Treatment with Anti-Tat Antibodies

Kaposi’s Sarcoma Lesion Progression in BKV-Tat Transgenic Mice Is Increased by Inflammatory Cytokines and Blocked by Treatment with Anti-Tat Antibodies

Pentosan Polysulfate as an Inhibitor of Extracellular HIV-1 Tat

Targeting HIV Transcription: The Quest for a Functional Cure

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