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31 results on '"Shtanko, Olena"'

2. Protein Interaction Mapping Identifies RBBP6 as a Negative Regulator of Ebola Virus Replication

Author

Batra, Jyoti, Hultquist, Judd F, Liu, Dandan, Shtanko, Olena, Von Dollen, John, Satkamp, Laura, Jang, Gwendolyn M, Luthra, Priya, Schwarz, Toni M, Small, Gabriel I, Arnett, Eusondia, Anantpadma, Manu, Reyes, Ann, Leung, Daisy W, Kaake, Robyn, Haas, Paige, Schmidt, Carson B, Schlesinger, Larry S, LaCount, Douglas J, Davey, Robert A, Amarasinghe, Gaya K, Basler, Christopher F, and Krogan, Nevan J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Biodefense, Biotechnology, Vaccine Related, Genetics, Emerging Infectious Diseases, Infectious Diseases, Prevention, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Carrier Proteins, Crystallography, X-Ray, DNA-Binding Proteins, Ebolavirus, HEK293 Cells, HeLa Cells, Hemorrhagic Fever, Ebola, Humans, Protein Interaction Mapping, Transcription Factors, Ubiquitin-Protein Ligases, Viral Proteins, Virus Replication, Hela Cells, Ebola virus, RBBP6, RNA viruses, VP30, antiviral factor, host-pathogen interactions, protein-protein interactions, virus-host interactions, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Ebola virus (EBOV) infection often results in fatal illness in humans, yet little is known about how EBOV usurps host pathways during infection. To address this, we used affinity tag-purification mass spectrometry (AP-MS) to generate an EBOV-host protein-protein interaction (PPI) map. We uncovered 194 high-confidence EBOV-human PPIs, including one between the viral transcription regulator VP30 and the host ubiquitin ligase RBBP6. Domain mapping identified a 23 amino acid region within RBBP6 that binds to VP30. A crystal structure of the VP30-RBBP6 peptide complex revealed that RBBP6 mimics the viral nucleoprotein (NP) binding to the same interface of VP30. Knockdown of endogenous RBBP6 stimulated viral transcription and increased EBOV replication, whereas overexpression of either RBBP6 or the peptide strongly inhibited both. These results demonstrate the therapeutic potential of biologics that target this interface and identify additional PPIs that may be leveraged for novel therapeutic strategies.

Published
2018

11. Chaperone-assisted selective autophagy targets filovirus VP40 as a client and restricts egress of virus particles.

Author

Jingjing Liang, Djurkovic, Marija A., Shtanko, Olena, and Harty, Ronald N.

Subjects
AUTOPHAGY, VIRUS-like particles, RECOMBINANT viruses, RAPAMYCIN
Abstract

The filovirus VP40 protein directs virion egress, which is regulated either positively or negatively by select VP40–host interactions. We demonstrate that host BAG3 and HSP70 recognize VP40 as a client and inhibit the egress of VP40 virus-like particles (VLPs) by promoting degradation of VP40 via Chaperone-assisted selective autophagy (CASA). Pharmacological inhibition of either the early stage formation of the VP40/ BAG3/HSP70 tripartite complex, or late stage formation of autolysosomes, rescued VP40 VLP egress back to WT levels. The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of autophagy, and we found that surface expression of EBOV GP on either VLPs or an infectious VSV recombinant virus, activated mTORC1. Notably, pharmacological suppression of mTORC1 signaling by rapamycin activated CASA in a BAG3-dependent manner to restrict the egress of both VLPs and infectious EBOV in Huh7 cells. In sum, our findings highlight the involvement of the mTORC1/ CASA axis in regulating filovirus egress. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Compound FC-10696 Inhibits Egress of Marburg Virus

Author

Han, Ziying, primary, Ye, Hong, additional, Liang, Jingjing, additional, Shepley-McTaggart, Ariel, additional, Wrobel, Jay E., additional, Reitz, Allen B., additional, Whigham, Alison, additional, Kavelish, Katrina N., additional, Saporito, Michael S., additional, Freedman, Bruce D., additional, Shtanko, Olena, additional, and Harty, Ronald N., additional

Published
2021
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13. Compound FC-10696 Inhibits Egress and Spread of Marburg Virus

Author

Han, Ziying, primary, Ye, Hong, additional, Liang, Jingjing, additional, Shepley-McTaggart, Ariel, additional, Wrobel, Jay E., additional, Reitz, Allen B., additional, Whigham, Alison, additional, Kavelish, Katrina N., additional, Saporito, Michael S., additional, Freedman, Bruce D., additional, Shtanko, Olena, additional, and Harty, Ronald N., additional

Published
2021
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15. Frontline Science: CD40 signaling restricts RNA virus replication in Mϕs, leading to rapid innate immune control of acute virus infection

Author

Rogers, Kai J, primary, Shtanko, Olena, additional, Stunz, Laura L, additional, Mallinger, Laura N, additional, Arkee, Tina, additional, Schmidt, Megan E, additional, Bohan, Dana, additional, Brunton, Bethany, additional, White, Judith M, additional, Varga, Steve M, additional, Butler, Noah S, additional, Bishop, Gail A, additional, and Maury, Wendy, additional

Published
2020
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16. Non-canonical proline-tyrosine interactions with multiple host proteins regulate Ebola virus infection

Author

Batra, Jyoti, primary, Anantpadma, Manu, additional, Small, Gabriel I., additional, Shtanko, Olena, additional, Zhang, Mengru, additional, Liu, Dandan, additional, Williams, Caroline G., additional, Biedenkopf, Nadine, additional, Becker, Stephan, additional, Gross, Michael L., additional, Leung, Daisy W., additional, Davey, Robert A., additional, Amarasinghe, Gaya K., additional, Krogan, Nevan J., additional, and Basler, Christopher F., additional

Published
2020
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18. Modular mimicry and engagement of the Hippo pathway by Marburg virus VP40: Implications for filovirus biology and budding

Author

Han, Ziying, primary, Dash, Shantoshini, additional, Sagum, Cari A., additional, Ruthel, Gordon, additional, Jaladanki, Chaitanya K., additional, Berry, Corbett T., additional, Schwoerer, Michael P., additional, Harty, Nina M., additional, Freedman, Bruce D., additional, Bedford, Mark T., additional, Fan, Hao, additional, Sidhu, Sachdev S., additional, Sudol, Marius, additional, Shtanko, Olena, additional, and Harty, Ronald N., additional

Published
2020
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21. Frontline Science: CD40 signaling restricts RNA virus replication in Mϕs, leading to rapid innate immune control of acute virus infection.

Author

Rogers, Kai J., Shtanko, Olena, Stunz, Laura L., Mallinger, Laura N., Arkee, Tina, Schmidt, Megan E., Bohan, Dana, Brunton, Bethany, White, Judith M., Varga, Steve M., Butler, Noah S., Bishop, Gail A., and Maury, Wendy

Subjects
VIRUS diseases, RNA viruses, VIRAL replication, EBOLA virus, VESICULAR stomatitis
Abstract

Many acute viral infections target tissue Mϕs, yet the mechanisms of Mϕ‐mediated control of viruses are poorly understood. Here, we report that CD40 expressed by peritoneal Mϕs restricts early infection of a broad range of RNA viruses. Loss of CD40 expression enhanced virus replication as early as 12–24 h of infection and, conversely, stimulation of CD40 signaling with an agonistic Ab blocked infection. With peritoneal cell populations infected with the filovirus, wild‐type (WT) Ebola virus (EBOV), or a BSL2 model virus, recombinant vesicular stomatitis virus encoding Ebola virus glycoprotein (rVSV/EBOV GP), we examined the mechanism conferring protection. Here, we demonstrate that restricted virus replication in Mϕs required CD154/CD40 interactions that stimulated IL‐12 production through TRAF6‐dependent signaling. In turn, IL‐12 production resulted in IFN‐γ production, which induced proinflammatory polarization of Mϕs, protecting the cells from infection. These CD40‐dependent events protected mice against virus challenge. CD40−/− mice were exquisitely sensitive to intraperitoneal challenge with a dose of rVSV/EBOV GP that was sublethal to CD40+/+ mice, exhibiting viremia within 12 h of infection and rapidly succumbing to infection. This study identifies a previously unappreciated role for Mϕ‐intrinsic CD40 signaling in controlling acute virus infection. [ABSTRACT FROM AUTHOR]

Published
2021
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22. Retro-2, a small molecule able to protect cells against a broad spectrum of menacing agents: Toxins, viruses, parasites and intracellular bacteria

Author

Tepshi, Livia, primary, Gupta, Neetu, additional, Noel, Romain, additional, Goudet, Amélie, additional, Hinsinger, Karen, additional, Michau, Aurélien, additional, Pons, Valérie, additional, Abdelkafi, Hajer, additional, Secher, Thomas, additional, Shima, Ayaka, additional, Shtanko, Olena, additional, Sakurai, Yasuteru, additional, Cojean, Sandrine, additional, Pomel, Sébastien, additional, Lievin-Le Moal, Vanessa, additional, Leignel, Véronique, additional, Herweg, Jo-Ana, additional, Fischer, Annette, additional, Johannes, Ludger, additional, Harrison, Kate, additional, Beard, Philippa M., additional, Rudel, Thomas, additional, Vacus, Joël, additional, Loiseau, Philippe M., additional, Davey, Robert A., additional, Oswald, Eric, additional, Cintrat, Jean-Christophe, additional, Barbier, Julien, additional, and Gillet, Daniel, additional

Published
2018
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23. Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Leishmania and Chlamydiales

Author

Gupta, Neetu, primary, Noël, Romain, additional, Goudet, Amélie, additional, Hinsinger, Karen, additional, Michau, Aurélien, additional, Pons, Valérie, additional, Abdelkafi, Hajer, additional, Secher, Thomas, additional, Shima, Ayaka, additional, Shtanko, Olena, additional, Sakurai, Yasuteru, additional, Cojean, Sandrine, additional, Pomel, Sébastien, additional, Liévin-Le Moal, Vanessa, additional, Leignel, Véronique, additional, Herweg, Jo-Ana, additional, Fischer, Annette, additional, Johannes, Ludger, additional, Harrison, Kate, additional, Beard, Philippa M., additional, Clayette, Pascal, additional, Le Grand, Roger, additional, Rayner, Jonathan O., additional, Rudel, Thomas, additional, Vacus, Joël, additional, Loiseau, Philippe M., additional, Davey, Robert A., additional, Oswald, Eric, additional, Cintrat, Jean-Christophe, additional, Barbier, Julien, additional, and Gillet, Daniel, additional

Published
2017
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24. Large-Scale Screening and Identification of Novel Ebola Virus and Marburg Virus Entry Inhibitors

Author

Anantpadma, Manu, primary, Kouznetsova, Jennifer, additional, Wang, Hang, additional, Huang, Ruili, additional, Kolokoltsov, Andrey, additional, Guha, Rajarshi, additional, Lindstrom, Aaron R., additional, Shtanko, Olena, additional, Simeonov, Anton, additional, Maloney, David J., additional, Maury, Wendy, additional, LaCount, Douglas J., additional, Jadhav, Ajit, additional, and Davey, Robert A., additional

Published
2016
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29. Integrating Interactome, Phenome, and Transcriptome Mapping Data for the C. elegans Germline

Author

Walhout, Albertha J.M., primary, Reboul, Jérôme, additional, Shtanko, Olena, additional, Bertin, Nicolas, additional, Vaglio, Philippe, additional, Ge, Hui, additional, Lee, Hongmei, additional, Doucette-Stamm, Lynn, additional, Gunsalus, Kristin C., additional, Schetter, Aaron J., additional, Morton, Diane G., additional, Kemphues, Kenneth J., additional, Reinke, Valerie, additional, Kim, Stuart K., additional, Piano, Fabio, additional, and Vidal, Marc, additional

Published
2002
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30. Acute PlasmodiumInfection Promotes Interferon-Gamma-Dependent Resistance to Ebola Virus Infection

Author

Rogers, Kai J., Shtanko, Olena, Vijay, Rahul, Mallinger, Laura N., Joyner, Chester J., Galinski, Mary R., Butler, Noah S., and Maury, Wendy

Abstract

During the 2013–2016 Ebola virus (EBOV) epidemic, a significant number of patients admitted to Ebola treatment units were co-infected with Plasmodium falciparum,a predominant agent of malaria. However, there is no consensus on how malaria impacts EBOV infection. The effect of acute Plasmodiuminfection on EBOV challenge was investigated using mouse-adapted EBOV and a biosafety level 2 (BSL-2) model virus. We demonstrate that acute Plasmodiuminfection protects from lethal viral challenge, dependent upon interferon gamma (IFN-γ) elicited as a result of parasite infection. Plasmodium-infected mice lacking the IFN-γ receptor are not protected. Ex vivoincubation of naive human or mouse macrophages with sera from acutely parasitemic rodents or macaques programs a proinflammatory phenotype dependent on IFN-γ and renders cells resistant to EBOV infection. We conclude that acute Plasmodiuminfection can safeguard against EBOV by the production of protective IFN-γ. These findings have implications for anti-malaria therapies administered during episodic EBOV outbreaks in Africa.

Published
2020
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31. Angiomotin regulates budding and spread of Ebola virus.

Author

Ziying Han, Ruthel, Gordon, Dash, Shantoshini, Berry, Corbett T., Freedman, Bruce D., Harty, Ronald N., and Shtanko, Olena

Subjects
*EBOLA virus, *EXTRACELLULAR matrix proteins, *VIRAL proteins, *ADAPTOR proteins, *VIRUS-like particles, *FLUORESCENCE microscopy, *CELL motility
Abstract

The Ebola virus (EBOV) VP40 matrix protein (eVP40) orchestrates assembly and budding of virions in part by hijacking selectWW-domain-bearing host proteins via its PPxY late (L)- domain motif. Angiomotin (Amot) is a multifunctional PPxYcontaining adaptor protein that regulates angiogenesis, actin dynamics, and cell migration/motility. Amot also regulates the Hippo signaling pathway via interactions with the WW-domain-containing Hippo effector protein Yes-associated protein (YAP). In this report, we demonstrate that endogenous Amot is crucial for positively regulating egress of eVP40 virus-like particles (VLPs) and for egress and spread of authentic EBOV. Mechanistically, we show that ectopic YAP expression inhibits eVP40 VLP egress and that Amot co-expression rescues budding of eVP40 VLPs in a dose-dependent and PPxY-dependent manner. Moreover, results obtained with confocal and total internal reflection fluorescence microscopy suggested that Amot's role in actin organization and dynamics also contributes to promoting eVP40-mediated egress. In summary, these findings reveal a functional and competitive interplay between virus and host proteins involving the multifunctional PPxY-containing adaptor Amot, which regulates both the Hippo pathway and actin dynamics. We propose that our results have wide-ranging implications for understanding the biology and pathology of EBOV infections. [ABSTRACT FROM AUTHOR]

Published
2020
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