MARIA ANELE ROMEO

Dottoressa di ricerca

ciclo: XXXIII



Titolo della tesi: HHV-6 DYSREGULATES AUTOPHAGY AND UPR IN THE INFECTED CELLS: IMPACT ON IMMUNE RESPOSE AND NEURODEGENERATIVE DISEASE

HHV-6A and HHV-6B are herpesviruses characterized by high level of homology, both isolated for the first time from immune-suppressed patients but able to infect different target cells. HHV-6B is the causative agent of exanthema subitum, a self-limiting disease that arises in young children, while no diseases have been shown to be caused by HHV-6A primary infection. These viruses are known to induce immune suppression and share the characteristic to be neurotropic, even if HHV6-A more efficiently replicate in neuronal cells compare to HHV-6B. However, HHV-6A and B have been associated with central nervous system (CNS) diseases, particularly a high number of HHV-6A viral copies have been found in the brains of patients suffering of Alzheimer’s disease (AD). Autophagy is a cellular process involved in several physiologic processes including immune response and CNS homeostasis. Although mostly of viruses, including Herpesviruses, have been shown to subvert autophagy to their own advantage, this PhD project reports for the first time that HHV-6A and HHV-6B are able to manipulate autophagy in the cells in which they replicate, and more importantly in monocytes in which this effect and the consequent ER stress induction prevents their differentiation into dendritic cells. Viral infection, in addition to ER stress, increased the level of intracellular ROS and activated STAT1 and STAT3 pathway, up-regulating PD-L1, to further induce immune dysfunction and favoring viral escape from immune recognition. Another consequence of autophagy dysregulation and ER stress/UPR induction by HHV-6A infection was the A accumulation and Tau protein hyperphosphorylation in astrocytes and primary neurons, which support a possible association of HHV-6A with AD. In conclusion this study evidences for that HHV-6A and HHV-6B infection has a strong impact on autophagy and ER stress/UPR in different cell types and that through this effect these viruses promote immune dysfunction and diseases.

Produzione scientifica

  • 11573/1026134 - 2017 - Metformin triggers apoptosis in PEL cells and alters bortezomib-induced Unfolded Protein Response increasing its cytotoxicity and inhibiting KSHV lytic cycle activation (01a Articolo in rivista)
    GRANATO, MARISA; GILARDINI MONTANI, MARIA SAVERIA; ROMEO, MARIA ANELE; SANTARELLI, ROBERTA; GONNELLA, ROBERTA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1026126 - 2017 - Bortezomib promotes KHSV and EBV lytic cycle by activating JNK and autophagy (01a Articolo in rivista)
    GRANATO, MARISA; ROMEO, MARIA ANELE; SANTARELLI, ROBERTA; GONNELLA, ROBERTA; GILARDINI MONTANI, MARIA SAVERIA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1671667 - 2022 - ATF6 prevents DNA damage and cell death in colon cancer cells undergoing ER stress (01a Articolo in rivista)
    BENEDETTI, ROSSELLA; ROMEO, MARIA ANELE; ARENA, ANDREA; GILARDINI MONTANI, MARIA SAVERIA; DI RENZO, LIVIA MARIA; CIRONE, MARA
  • 11573/1671685 - 2023 - Different outcome of targeting ERN1/IRE1 alpha and EIF2AK3/PERK in NSG mice engrafted with primary effusion lymphoma (01f Lettera, Nota)
    ARENA, ANDREA; ROMEO, MARIA ANELE; ANASTASIADOU, ELENI; TRIVEDI, PANKAJ; GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; SANTARELLI, ROBERTA; GONNELLA, ROBERTA; MARCHESE, CINZIA; MASUELLI, LAURA; CIRONE, MARA
  • 11573/895980 - 2016 - Concomitant reduction of c-Myc expression and PI3K/AKT/mTOR signaling by quercetin induces a strong cytotoxic effect against Burkitt's lymphoma (01a Articolo in rivista)
    GRANATO, MARISA; ROMEO, MARIA ANELE; YADAV, SHIVANGI; SANTARELLI, ROBERTA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1212285 - 2019 - Impact of HHV-6A and HHV-6B lytic infection on autophagy and endoplasmic reticulum stress (01a Articolo in rivista)
    ROMEO, MARIA ANELE; MASUELLI, LAURA; GAETA, AURELIA; NAZZARI, CRISTINA; GRANATO, MARISA; GILARDINI MONTANI, MARIA SAVERIA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1277319 - 2019 - Could autophagy dysregulation link neurotropic viruses to Alzheimer's disease? (01a Articolo in rivista)
    ROMEO, MARIA ANELE; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1277323 - 2019 - Mutant p53, stabilized by its interplay with HSP90, activates a positive feed-back loop between NRF2 and p62 that induces chemio-resistance to Apigenin in pancreatic cancer cells (01a Articolo in rivista)
    GILARDINI MONTANI, MARIA SAVERIA; GRANATO, MARISA; ROMEO, MARIA ANELE; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1277339 - 2019 - Stat3 phosphorylation affects p53/p21 axis and KSHV lytic cycle activation (01a Articolo in rivista)
    SANTARELLI, ROBERTA; ROMEO, MARIA ANELE; GAETA, AURELIA; NAZZARI, CRISTINA; GONNELLA, ROBERTA; GRANATO, MARISA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1353969 - 2019 - Quercetin interrupts the positive feedback loop between STAT3 and IL-6, promotes autophagy, and reduces ROS, preventing EBV-driven B cell immortalization (01a Articolo in rivista)
    GRANATO, MARISA; GILARDINI MONTANI, MARIA SAVERIA; ZOMPETTA, CLAUDIA; SANTARELLI, ROBERTA; GONNELLA, ROBERTA; ROMEO, MARIA ANELE; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1353967 - 2019 - HHV-6B reduces autophagy and induces ER stress in primary monocytes impairing their survival and differentiation into dendritic cells (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; GAETA, AURELIA; NAZZARI, CRISTINA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1374144 - 2020 - HHV-6A infection dysregulates autophagy/UPR interplay increasing beta amyloid production and tau phosphorylation in astrocytoma cells as well as in primary neurons, possible molecular mechanisms linking viral infection to Alzheimer's disease (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; GAETA, AURELIA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1426937 - 2020 - KSHV dysregulates bulk macroautophagy, mitophagy and UPR to promote endothelial to mesenchymal transition and CCL2 release, key events in viral-driven sarcomagenesis (01a Articolo in rivista)
    SANTARELLI, ROBERTA; GILARDINI MONTANI, MARIA SAVERIA; ROMEO, MARIA ANELE; GAETA, AURELIA; GONNELLA, ROBERTA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1410146 - 2020 - KSHV infection skews macrophage polarisation towards M2-like/TAM and activates Ire1 α-XBP1 axis up-regulating pro-tumorigenic cytokine release and PD-L1 expression (01a Articolo in rivista)
    GILARDINI MONTANI, MARIA SAVERIA; SANTARELLI, ROBERTA; GRANATO, MARISA; ROMEO, MARIA ANELE; GONNELLA, ROBERTA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1410107 - 2020 - PBA preferentially impairs cell survival of glioblastomas carrying mutp53 by reducing its expression level, stabilizing wtp53, downregulating the mevalonate kinase and dysregulating UPR (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; CIRONE, MARA
  • 11573/1447617 - 2020 - STAT3 and mutp53 Engage a Positive Feedback Loop Involving HSP90 and the Mevalonate Pathway (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; SANTARELLI, ROBERTA; CIRONE, MARA
  • 11573/1542828 - 2021 - The cross-talk between STAT1/STAT3 and ROS up-regulates PD-L1 and promotes the release of pro-inflammatory/immune suppressive cytokines in primary monocytes infected by HHV-6B (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; GAETA, AURELIA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1542820 - 2021 - p53-R273H Sustains ROS, Pro-Inflammatory Cytokine Release and mTOR Activation While Reducing Autophagy, Mitophagy and UCP2 Expression, Effects Prevented by wtp53 (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; ARENA, ANDREA; CIRONE, MARA
  • 11573/1542801 - 2021 - Ire1 alpha/xbp1 axis sustains primary effusion lymphoma cell survival by promoting cytokine release and stat3 activation (01a Articolo in rivista)
    GONNELLA, ROBERTA; GILARDINI MONTANI, MARIA SAVERIA; GUTTIERI, LUISA; ROMEO, MARIA ANELE; SANTARELLI, ROBERTA; CIRONE, MARA
  • 11573/1551365 - 2021 - PGE2 released by pancreatic cancer cells undergoing ER stress transfers the stress to DCs impairing their immune function (01a Articolo in rivista)
    GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; PICONESE, SILVIA; PULCINELLI, FABIO MARIA; ROMEO, MARIA ANELE; MASUELLI, LAURA; CIRONE, MARA
  • 11573/1546732 - 2020 - Viral Infection and Autophagy Dysregulation. The Case of HHV-6, EBV and KSHV (01g Articolo di rassegna (Review))
    ROMEO, MARIA ANELE; SANTARELLI, ROBERTA; GILARDINI MONTANI, MARIA SAVERIA; GONNELLA, ROBERTA; BENEDETTI, ROSSELLA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1577796 - 2021 - Role of upr sensor activation in cell death–survival decision of colon cancer cells stressed by dpe treatment (01a Articolo in rivista)
    BENEDETTI, ROSSELLA; GILARDINI MONTANI, MARIA SAVERIA; ROMEO, MARIA ANELE; ARENA, ANDREA; SANTARELLI, ROBERTA; CIRONE, MARA
  • 11573/1577880 - 2021 - Lovastatin reduces PEL cell survival by phosphorylating ERK1/2 that blocks the autophagic flux and engages a cross-talk with p53 to activate p21 (01a Articolo in rivista)
    SANTARELLI, ROBERTA; GILARDINI MONTANI, MARIA SAVERIA; ROMEO, MARIA ANELE; GONNELLA, ROBERTA; CIRONE, MARA
  • 11573/1581319 - 2021 - Anticancer effect of AZD2461 PARP inhibitor against colon cancer cells carrying wt or dysfunctional p53 (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; ARENA, ANDREA; CIRONE, MARA
  • 11573/1587456 - 2022 - DNA damage triggers an interplay between wtp53 and c-Myc affecting lymphoma cell proliferation and Kaposi sarcoma herpesvirus replication (01a Articolo in rivista)
    ARENA, ANDREA; GILARDINI MONTANI, MARIA SAVERIA; ROMEO, MARIA ANELE; BENEDETTI, ROSSELLA; GAETA, AURELIA; CIRONE, MARA
  • 11573/1587474 - 2021 - New insights into curcumin-and resveratrol-mediated anti-cancer effects (01a Articolo in rivista)
    ARENA, ANDREA; ROMEO, MARIA ANELE; BENEDETTI, ROSSELLA; MASUELLI, LAURA; GILARDINI MONTANI, MARIA SAVERIA; CIRONE, MARA
  • 11573/1614983 - 2022 - VPA and TSA Interrupt the Interplay between mutp53 and HSP70, Leading to CHK1 and RAD51 Down-Regulation and Sensitizing Pancreatic Cancer Cells to AZD2461 PARP Inhibitor (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; ARENA, ANDREA; CIRONE, MARA
  • 11573/1627726 - 2022 - The dysregulation of autophagy and ER stress induced by HHV-6A infection activates pro-inflammatory pathways and promotes the release of inflammatory cytokines and cathepsin S by CNS cells (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; BENEDETTI, ROSSELLA; ARENA, ANDREA; GAETA, AURELIA; CIRONE, MARA
  • 11573/1640535 - 2022 - p62/SQSTM1 promotes mitophagy and activates the NRF2-mediated antioxidant and anti-inflammatory response restraining EBV-driven B lymphocyte proliferation (01a Articolo in rivista)
    GILARDINI MONTANI, MARIA SAVERIA; SANTARELLI, ROBERTA; GONNELLA, ROBERTA; ROMEO, MARIA ANELE; BENEDETTI, ROSSELLA; ARENA, ANDREA; FAGGIONI, ALBERTO; CIRONE, MARA
  • 11573/1640499 - 2022 - Targeting c-Myc Unbalances UPR towards Cell Death and Impairs DDR in Lymphoma and Multiple Myeloma Cells (01a Articolo in rivista)
    ARENA, ANDREA; ROMEO, MARIA ANELE; BENEDETTI, ROSSELLA; GILARDINI MONTANI, MARIA SAVERIA; CIRONE, MARA
  • 11573/1640511 - 2022 - The impairment of DDR reduces XBP1s, further increasing DNA damage, and triggers autophagy via PERK/eIF2alpha in MM and IRE1alpha/JNK1/2 in PEL cells (01a Articolo in rivista)
    ARENA, ANDREA; ROMEO, MARIA ANELE; BENEDETTI, ROSSELLA; GILARDINI MONTANI, MARIA SAVERIA; CIRONE, MARA
  • 11573/1659741 - 2022 - Concomitant Inhibition of IRE1α/XBP1 Axis of UPR and PARP: A Promising Therapeutic Approach against c-Myc and Gammaherpesvirus-Driven B-Cell Lymphomas (01a Articolo in rivista)
    BENEDETTI, ROSSELLA; ARENA, ANDREA; ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; GONNELLA, ROBERTA; SANTARELLI, ROBERTA; TRIVEDI, PANKAJ; CIRONE, MARA
  • 11573/1659739 - 2022 - c-Myc Sustains Pancreatic Cancer Cell Survival and mutp53 Stability through the Mevalonate Pathway (01a Articolo in rivista)
    ROMEO, MARIA ANELE; GILARDINI MONTANI, MARIA SAVERIA; ARENA, ANDREA; BENEDETTI, ROSSELLA; CIRONE, MARA
  • 11573/1325331 - 2019 - Kaposi Sarcoma Herpes Virus (KSHV) infection inhibits macrophage formation and survival by counteracting Macrophage Colony-Stimulating Factor (M-CSF)-induced increase of Reactive Oxygen Species (ROS), c-Jun N-terminal kinase (JNK) phosphorylation and autophagy (01a Articolo in rivista)
    GILARDINI MONTANI, MARIA SAVERIA; SANTARELLI, ROBERTA; ROMEO, MARIA ANELE; GRANATO, MARISA; FAGGIONI, ALBERTO; CIRONE, MARA

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