Autophagy is a catabolic pathway that helps cells to survive under stressful conditions. Cells also use autophagy clear microbiological infections, but microbes have learned how manipulate the autophagic for their own benefit. The experimental evidence obtained in this study suggests flux blocked at final steps during reactivation of Epstein-Barr virus (EBV) from latency. This indicated by level lipidated form LC3 does not increase presence bafilomycin and lack colocalization autophagosomes...

EBV has been reported to impair monocyte in vitro differentiation into dendritic cells (DCs) and reduce cell survival. In this study, we added another layer of knowledge topic showed that these effects correlated with macroautophagy/autophagy, ROS mitochondrial biogenesis reduction. Of note, autophagy ROS, although strongly interconnected, have separately be induced by CSF2/GM-CSF (colony stimulating factor 2) required for CSF2-IL4-driven DCs. We show infects monocytes initiates a feedback...

Heat-shock protein (HSP) 70 is aberrantly expressed in different malignancies and has a cancer-specific cell-protective effect. As such, it emerged as promising target for anticancer therapy. In this study, the effect of HSP70-specific inhibitor (PES), also Pifitrin-μ, on primary effusion lymphoma (PEL) cell viability was analyzed. PES treatment induced dose- time-dependent cytotoxic BC3 BCBL1 PEL cells by inducing lysosome membrane permeabilization, relocation cathepsin D cytosol, Bid...

Kaposis's sarcoma associated herpesvirus (KSHV) has been reported to infect, among others, monocytes and dendritic cells DCs impairing their function. However, the underlying mechanisms remain not completely elucidated yet. Here we show that DC exposure active or UV-inactivated KSHV resulted in STAT3 phosphorylation. This effect, partially dependent on KSHV-engagement of DC-SIGN, induced a high release IL-10, IL-6 IL-23, cytokines turn might maintain phosphorylated state. activation also...

Apigenin is a flavonoid widely distributed in plant kingdom that exerts cytotoxic effects against variety of solid and haematological cancers. In this study, we investigated the effect apigenin primary effusion lymphoma (PEL), KSHV-associated B cell characterized by very aggressive behavior, displaying constitutive activation STAT3 as well other oncogenic pathways harboring wtp53. Cell death was assessed trypan blue exclusion assay, FACS analysis biochemical studies. The latter were also...

Pancreatic cancer is one of the most aggressive cancers whose prognosis worsened by poor response to current chemotherapies. In this study, we investigated cytotoxic effect Apigenin, against two pancreatic cell lines, namely Panc1 and PaCa44, harboring different p53 mutations. Apigenin a flavonoid widely distributed in nature that displays anti-inflammatory anticancer properties variety cancers. Here observed exerted stronger line comparison PaCa44. Searching for mechanisms responsible such...

We have reported in the accompanying paper that BFRF1 protein of Epstein-Barr virus (EBV) is important for efficient primary viral envelopment and egress (A. Farina, R. Feederle, S. Raffa, Gonnella, Santarelli, L. Frati, A. Angeloni, M. Torrisi, Faggioni, H.-J. Delecluse, J. Virol. 79:3703-3712). Here we describe characterization product EBV BFLF2 gene, which belongs to a family conserved herpesviral genes include UL31 herpes simplex pseudorabies whose products are known interact with UL34,...

Previous genetic and biochemical studies performed with several members of the Alphaherpesvirus subfamily have shown that UL31 UL34 proteins are essential components molecular machinery mediates primary egress newly assembled capsids across nuclear membrane. Further, there is substantial evidence BFLF2 BFRF1, respective positional homologs in Epstein-Barr virus (EBV) genome, also their functional homologs, i.e., UL31/UL34 pathway common to distant herpesviruses. However, low degree protein...

Type 2 is the type of diabetes with higher prevalence in contemporary time, representing about 90% global cases diabetes. In course diabetes, several complications can occur, mostly due to hyperglycemia and increased reactive oxygen species (ROS) production. One them represented by an susceptibility microbial infections a reduced capacity clear them. Therefore, knowing impact on immune system functionality utmost importance for management disease. this study, we show that medium containing...

Autophagy is usually a pro-survival mechanism in cancer cells, especially the course of chemotherapy, thus autophagy inhibition may enhance chemotherapy-mediated anti-cancer effect. However, since strongly involved immunogenicity cell death by promoting ATP release, its reduce immune response against tumors, negatively influencing overall outcome chemotherapy. In this study, we evaluated vitro and vivo effect curcumin (CUR) Her2/neu overexpressing breast cells (TUBO) presence or absence...

Understanding the mechanisms of autophagy induction and its role during chemotherapeutic treatments is fundamental importance in order to manipulate it improve outcome chemotherapy. In particular whether bortezomib-induced plays a pro-survival or pro-death still controversial. this study we investigated if bortezomib induced endoplasmic reticulum (ER) stress activated Primary Effusion Lymphoma (PEL) cells how they influenced cell survival. We found that up-regulation ER molecules BIP CHOP...

Optimal tumor eradication often results from the death of malignant cells, as induced by chemotherapeutic agents, coupled to induction antitumor immune responses. However, cancer cells frequently become resistant cytotoxic activity chemotherapy. The aim present study was evaluate whether zinc dichloride (ZnCl2), which known re-establish chemosensitivity reactivating p53, promotes immunogenic instances cell death. We found that ZnCl2, in combination with agents such cisplatin and adriamycin...

This study confirms that autophagy is activated concomitantly with KSHV lytic cycle induction, and inhibition by BECN1 knockdown reduces viral gene expression. In addition, we extend previous observations show blocked at late steps, during replication. indicated the lack of colocalization autophagosomes lysosomes LC3-II level does not increase in presence bafilomycin A1 primary effusion lymphoma (PEL) cells induced to enter cycle, either TPA/sodium butyrate (BC3 BCBL1) or doxycycline...

KSHV and EBV are gammaherpesviruses strictly linked to human cancers. Even if the majority of cancer cells harbor a latent infection, few that undergo viral replication may contribute pathogenesis maintenance virus-associated malignancies. Cytotoxic drugs used for therapies cancers harboring virus-infection often have, as side effect, activation lytic cycle. Therefore it is important investigate whether they affect reactivation understand underlying mechanisms involved. In this study, we...

The oncogenic gammaherpesvirus Epstein–Barr virus (EBV) immortalizes in vitro B lymphocytes into lymphoblastoid cell lines (LCLs), a model that gives the opportunity to explore molecular mechanisms driving viral tumorigenesis. In this study, we addressed potential of quercetin, widely distributed flavonoid displaying antioxidant, anti-inflammatory, and anti-cancer properties, preventing EBV-driven immortalization. results obtained indicated quercetin inhibited thectivation signal transducer...

Abstract Background Kaposi’s Sarcoma Herpesvirus (KSHV) is a gammaherpesvirus strongly linked to human cancer. The virus also able induce immune suppression, effect that contributes onset/progression of the viral-associated malignancies. As KSHV may infect macrophages and these cells abundantly infiltrate sarcoma lesions, in this study we investigated whether KSHV-infection could affect macrophage polarisation promote tumorigenesis. Methods FACS analysis was used detect markers PD-L1...

We report the identification and characterization of p33, product Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 69 (ORF69), a positional homolog conserved protein UL31. p33 is expressed upon induction viral lytic cycle with early kinetics. Immunofluorescence analysis revealed that in infected cell lines, localized nucleus, both dotted spots along nuclear membrane. Nuclear fractionation experiments showed partitions matrix, immunoblotting purified virions immunoelectron...

// Marisa Granato 1 , Maria Saveria Gilardini Montani Mariarosari Filardi Alberto Faggioni 1, * Mara Cirone Department of Experimental Medicine, Sapienza University Rome. 00161 Rome, Italy Correspondence to: Cirone, e-mail: mara.cirone@uniroma1.it Faggioni, alberto.faggioni@uniroma1.it Keywords: capsaicin, Immunogenic cell death, STAT3, DCs, PEL Received: June 05, 2015      Accepted: August 07, Published: 18, 2015 ABSTRACT Capsaicin, the pungent alkaloid red pepper...

Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway regulates multiple cellular processes such as cell proliferation, evasion from apoptosis, migration, glucose metabolism, protein synthesis and proper differentiation in immune cells. Kaposi sarcoma-associated herpesvirus (KSHV), an oncogenic virus associated with several human malignancies, expresses a variety latent lytic proteins able to activate PI3K/AKT pathway, promoting the growth infected...

We have previously shown that Kaposi sarcoma-associated herpesvirus (KSHV) impairs monocyte differentiation into dendritic cells (DCs). Macroautophagy/autophagy has been reported to be essential in such a differentiating process. Here we extended these studies and found the impairment of DC formation by KSHV occurs through autophagy inhibition. indeed reduces CAST (calpastatin) consequently decreases ATG5 expression both THP-1 monocytoid primary monocytes. unveiled new mechanism put place...

Abstract Programmed death ligand 1 (PD-L1) (also called B7-H1) is a membrane immune-modulatory protein whose overexpression on the surface of tumor cells as well APCs impairs T-cell-mediated killing. Viruses that establish chronic infections have developed number strategies to escape from immune recognition including up-regulation PD-L1. This study shows for first time human oncovirus EBV infects primary monocytes using HLA-DR and induced strong PD-L1 expression their surface. Searching...