Inhibition of HIV-1 replication in primary human monocytes by the IκB-αS32/36A repressor of NF-κB

Palmieri, Camillo; Trimboli, Francesca; Puca, Antimina; Fiume, Giuseppe; Scala, Giuseppe; Quinto, Ileana

doi:10.1186/1742-4690-1-45

Cited by 16 publications

(9 citation statements)

References 24 publications

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“…HIV-1 enters monocytes by classical binding and fusion using CD4 receptor and CCR5 co-receptor. HIV-1 undergoes reverse transcription, but robust virion release does not occur in monocytes [16-18]. As monocytes differentiate to macrophages, they become more susceptible to productive HIV-1 replication through mechanism(s) that are not entirely clear or well integrated within each other.…”

Section: Introductionmentioning

confidence: 99%

“…As monocytes differentiate to macrophages, they become more susceptible to productive HIV-1 replication through mechanism(s) that are not entirely clear or well integrated within each other. A number of mechanisms have been proposed to explain the refractory nature of monocytes to productive HIV-1 replication [13] [10, 14, 15] [16] [17, 18] [19-22]. Initially, lower expression of CCR5 was thought to restrict HIV-1 entry into monocytes [15, 23].…”

Section: Introductionmentioning

confidence: 99%

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β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

Aljawai¹,

Richards²,

Seaton³

et al. 2014

CHR

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Cells of the monocyte/macrophage lineage are an important target for HIV-1 infection. They are often at anatomical sites linked to HIV-1 transmission and are an important vehicle for disseminating HIV-1 throughout the body, including the central nervous system. Monocytes do not support extensive productive HIV-1 replication, but they become more susceptible to HIV-1 infection as they differentiate into macrophages. The mechanisms guiding susceptibility of HIV-1 replication in monocytes versus macrophages are not entirely clear. We determined whether endogenous activity of β-catenin signaling impacts differential susceptibility of monocytes and monocyte-derived macrophages (MDMs) to productive HIV-1 replication. We show that monocytes have an approximately 4-fold higher activity of β-catenin signaling than MDMs. Inducing β-catenin in MDMs suppressed HIV-1 replication by 5-fold while inhibiting endogenous β-catenin signaling in monocytes by transfecting with a dominant negative mutant for the downstream effector of β-catenin (TCF-4) promoted productive HIV-1 replication by 6-fold. These findings indicate that β-catenin/TCF-4 is an important pathway for restricted HIV-1 replication in monocytes and plays a significant role in potentiating HIV-1 replication as monocytes differentiate into macrophages. Targeting this pathway may provide a novel strategy to purge the latent reservoir from monocytes/macrophages, especially in sanctuary sites for HIV-1 such as the central nervous system.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

Aljawai¹,

Richards²,

Seaton³

et al. 2014

CHR

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“…SP interacting with the FL NK-1R leads to downstream up-regulation of NF-κB dependent gene products (Lai et al 2008b). NF-κB transacting factors enhance HIV/SIV expression in lymphoid and monocytes (Palmieri et al 2004), and reactivate latent HIV in hematopoietic progenitor cells (McNamara et al 2012). Since NK-1R antagonists can block the effects of SP, and aprepitant can cross the blood-brain barrier, it may be useful as an antiviral strategy to reduce viral burden in the CNS (Tebas et al 2011, Douglas and Leeman 2011).…”

Section: Discussionmentioning

confidence: 99%

Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor

et al. 2013

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The associations between the neurokinin-1 receptor (NK-1R), substance P (SP), and HIV-1 were investigated in neurosphere-derived cultures of microglial-depleted human fetal brain cells (HFBC). Full-length NK-1R was identified in HFBC cultures. SP treatment of the HFBC increased intracellular calcium mobilization and decreased electrical impedance, both of which were blocked by the NK-1R antagonist aprepitant. SP treatment of HIV-1-infected HFBC up-regulated HIV-1 expression. These data show that human neural cells grown from neurospheres express functional full length NK-1R that is responsive to SP, and that SP enhanced HIV-1 infection in HBFC.

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“…Peripheral blood mononuclear cells were isolated from healthy donors by Ficoll-Paque gradient centrifugation (GE Healthcare Life Sciences, Piscataway, NJ, USA), as previously described (27-29). Primary cultured NK cell populations were obtained from 10-day co-cultures of PBMCs with irradiated Epstein-Barr virus-positive RPMI 8866 lymphoblastoid cell line, as previously described (30).…”

Section: Methodsmentioning

confidence: 99%

Cancer-Associated CD43 Glycoforms as Target of Immunotherapy

Tuccillo

Palmieri

Fiume

et al. 2014

Molecular Cancer Therapeutics

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CD43 is a sialoglycosylated membrane protein that is involved in cell proliferation and differentiation. CD43 glycoforms that are recognized by the UN1 monoclonal antibody (mAb) were expressed in lymphoblastoid T-cell lines and solid tumors, such as breast, colon, gastric, and squamous cell lung carcinomas, while unexpressed in the normal counterparts. The cancer–association of UN1/CD43 epitope suggested the possibility to use the UN1 mAb for tumor diagnosis and therapy. In this study, we show that the UN1 mAb was endowed with anti-tumor activity in vivo since its passive transfer inhibited the growth of UN1-positive HPB-ALL lymphoblastoid T-cells in mice. Further, we demonstrate that tumor inhibition was due to UN1 mAb-dependent NK-mediated cytotoxicity. By screening a phage displayed random peptide library we identified the phagotope 2/165 as a mimotope of the UN1 antigen, as it harboured a peptide sequence that was specifically recognized by the UN1 mAb and inhibited the binding of the UN1 mAb to UN1-positive tumour cells. Based on sequence homology with the extracellular region of CD43 (amino acids 64 to 83), the 2/165 peptide sequence was likely mimicking the protein core of the UN1/CD43 epitope. When used as vaccine in mice, the 2/165 phagotope raised antibodies against the UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen structure, and could represent a novel immunogen for cancer immunotherapy. These findings support the feasibility to use monoclonal antibodies to identify cancer-associated mimotopes for immunotherapy.

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Inhibition of HIV-1 replication in primary human monocytes by the IκB-αS32/36A repressor of NF-κB

Cited by 16 publications

References 24 publications

β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor

Cancer-Associated CD43 Glycoforms as Target of Immunotherapy

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Inhibition of HIV-1 replication in primary human monocytes by the IκB-αS32/36A repressor of NF-κB

Cited by 16 publications

References 24 publications

&#946;-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

&#946;-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor

Cancer-Associated CD43 Glycoforms as Target of Immunotherapy

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β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection