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2. Envelope protein ubiquitination drives entry and pathogenesis of Zika virus

Author

Giraldo, Maria I, Xia, Hongjie, Aguilera-Aguirre, Leopoldo, Hage, Adam, van Tol, Sarah, Shan, Chao, Xie, Xuping, Sturdevant, Gail L, Robertson, Shelly J, McNally, Kristin L, Meade-White, Kimberly, Azar, Sasha R, Rossi, Shannan L, Maury, Wendy, Woodson, Michael, Ramage, Holly, Johnson, Jeffrey R, Krogan, Nevan J, Morais, Marc C, Best, Sonja M, Shi, Pei-Yong, and Rajsbaum, Ricardo

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Emerging Infectious Diseases, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Brain, Cell Line, Culicidae, Endosomes, Female, Hepatitis A Virus Cellular Receptor 1, Humans, Male, Membrane Fusion, Mice, Organ Specificity, Polyubiquitin, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Ubiquitination, Viral Envelope Proteins, Viral Tropism, Viremia, Virus Internalization, Virus Replication, Zika Virus, Zika Virus Infection, General Science & Technology
Abstract

Zika virus (ZIKV) belongs to the family Flaviviridae, and is related to other viruses that cause human diseases. Unlike other flaviviruses, ZIKV infection can cause congenital neurological disorders and replicates efficiently in reproductive tissues1-3. Here we show that the envelope protein (E) of ZIKV is polyubiquitinated by the E3 ubiquitin ligase TRIM7 through Lys63 (K63)-linked polyubiquitination. Accordingly, ZIKV replicates less efficiently in the brain and reproductive tissues of Trim7-/- mice. Ubiquitinated E is present on infectious virions of ZIKV when they are released from specific cell types, and enhances virus attachment and entry into cells. Specifically, K63-linked polyubiquitin chains directly interact with the TIM1 (also known as HAVCR1) receptor of host cells, which enhances virus entry in cells as well as in brain tissue in vivo. Recombinant ZIKV mutants that lack ubiquitination are attenuated in human cells and in wild-type mice, but not in live mosquitoes. Monoclonal antibodies against K63-linked polyubiquitin specifically neutralize ZIKV and reduce viraemia in mice. Our results demonstrate that the ubiquitination of ZIKV E is an important determinant of virus entry, tropism and pathogenesis.

Published
2020

8. Abstract 3245: AXL as a therapeutic target in STK11 mutant NSCLC

Author

Blø, Magnus, primary, Rayford, Austin, additional, Madeleine, Noëlly, additional, Gärtner, Fabian, additional, Bohan, Dana, additional, Ruggio, Natalie, additional, Li, Huiyu, additional, Girard, Luc, additional, Brekken, Rolf, additional, Minna, John, additional, Ånerud, Marianne, additional, Maury, Wendy, additional, Gorcea-Carson, Claudia, additional, Gausdal, Gro, additional, Micklem, David R., additional, and McCracken, Nigel, additional

Published
2023
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9. Structurally Different Yet Functionally Similar: Aptamers Specific for the Ebola Virus Soluble Glycoprotein and GP1,2 and Their Application in Electrochemical Sensing

Author

Banerjee, Soma, primary, Hemmat, Mahsa Askary, additional, Shubham, Shambhavi, additional, Gosai, Agnivo, additional, Devarakonda, Sivaranjani, additional, Jiang, Nianyu, additional, Geekiyanage, Charith, additional, Dillard, Jacob A., additional, Maury, Wendy, additional, Shrotriya, Pranav, additional, Lamm, Monica H., additional, and Nilsen-Hamilton, Marit, additional

Published
2023
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19. Human Organotypic Airway and Lung Organoid Cells of Bronchiolar and Alveolar Differentiation Are Permissive to Infection by Influenza and SARS-CoV-2 Respiratory Virus

Author

Ekanger, Camilla Tvedt, primary, Zhou, Fan, additional, Bohan, Dana, additional, Lotsberg, Maria Lie, additional, Ramnefjell, Maria, additional, Hoareau, Laurence, additional, Røsland, Gro Vatne, additional, Lu, Ning, additional, Aanerud, Marianne, additional, Gärtner, Fabian, additional, Salminen, Pirjo Riitta, additional, Bentsen, Mariann, additional, Halvorsen, Thomas, additional, Ræder, Helge, additional, Akslen, Lars A., additional, Langeland, Nina, additional, Cox, Rebecca, additional, Maury, Wendy, additional, Stuhr, Linda Elin Birkhaug, additional, Lorens, James B., additional, and Engelsen, Agnete S. T., additional

Published
2022
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20. Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein

Author

Van Ert, Hanora A., primary, Bohan, Dana W., additional, Rogers, Kai, additional, Fili, Mohammad, additional, Rojas Chávez, Roberth A., additional, Qing, Enya, additional, Han, Changze, additional, Dempewolf, Spencer, additional, Hu, Guiping, additional, Schwery, Nathan, additional, Sevcik, Kristina, additional, Ruggio, Natalie, additional, Boyt, Devlin, additional, Pentella, Michael A., additional, Gallagher, Tom, additional, Jackson, J. Brooks, additional, Merrill, Anna E., additional, Knudson, C. Michael, additional, Brown, Grant D., additional, Maury, Wendy, additional, and Haim, Hillel, additional

Published
2022
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21. Phosphatidylserine receptors enhance SARS-CoV-2 infection

Author

Bohan, Dana, primary, Van Ert, Hanora, additional, Ruggio, Natalie, additional, Rogers, Kai J., additional, Badreddine, Mohammad, additional, Aguilar Briseño, José A., additional, Elliff, Jonah M., additional, Rojas Chavez, Roberth Anthony, additional, Gao, Boning, additional, Stokowy, Tomasz, additional, Christakou, Eleni, additional, Kursula, Petri, additional, Micklem, David, additional, Gausdal, Gro, additional, Haim, Hillel, additional, Minna, John, additional, Lorens, James B., additional, and Maury, Wendy, additional

Published
2021
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24. Limited variation between SARS-CoV-2-infected individuals in domain specificity and relative potency of the antibody response against the spike glycoprotein

Author

Van Ert, Hanora A., primary, Bohan, Dana W., additional, Rogers, Kai, additional, Fili, Mohammad, additional, Rojas Chávez, Roberth A., additional, Qing, Enya, additional, Han, Changze, additional, Dempewolf, Spencer, additional, Hu, Guiping, additional, Schwery, Nathan, additional, Sevcik, Kristina, additional, Ruggio, Natalie, additional, Boyt, Devlin, additional, Pentella, Michael A., additional, Gallagher, Tom, additional, Jackson, J. Brooks, additional, Merrill, Anna E., additional, Knudson, C. Michael, additional, Brown, Grant D., additional, Maury, Wendy, additional, and Haim, Hillel, additional

Published
2021
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26. Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19

Author

Bohan, Dana, primary, Van Ert, Hanora, additional, Ruggio, Natalie, additional, Rogers, Kai J., additional, Badreddine, Mohammad, additional, Aguilar Briseño, José A., additional, Chavez, Roberth Anthony Rojas, additional, Gao, Boning, additional, Stokowy, Tomasz, additional, Christakou, Eleni, additional, Micklem, David, additional, Gausdal, Gro, additional, Haim, Hillel, additional, Minna, John, additional, Lorens, James B., additional, and Maury, Wendy, additional

Published
2021
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27. Optimizing immunoassay-based selection of donors for COVID-19 convalescent plasma

Author

Van Ert, Hanora A, primary, Rogers, Kai, additional, Bohan, Dana, additional, Han, Chanze, additional, Dempewolf, Spencer, additional, Sevcik, Kristina, additional, Ruggio, Natalie, additional, Rojas-Chavez, Anthony, additional, Boyt, Devlin, additional, Pentella, Michael, additional, Jackson, Brooks, additional, Merrill, Anna, additional, Knudson, Michael, additional, Maury, Wendy, additional, and Haim, Hillel, additional

Published
2021
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29. DNA Aptamers for Early Detection of Ebolavirus

Author

Banerjee, Soma, primary, Hoinka, Jan, additional, Gosai, Agnivo, additional, Zhu, Zhichen, additional, Devarakonda, Sivaranjani, additional, Geekiyanage, Charith, additional, Shubham, Shambhavi, additional, Lennemann, Nicholas, additional, Dillard, Jake, additional, Ruggio, Natalie, additional, Przytycka, Teresa, additional, Maury, Wendy, additional, Shrotriya, Pranav, additional, and Nilsen‐Hamilton, Marit, additional

Published
2021
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30. Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation

Author

Vijay, Rahul, primary, Guthmiller, Jenna J., additional, Sturtz, Alexandria J., additional, Crooks, Sequoia, additional, Johnson, Jordan T., additional, Li, Lei, additional, Lan, Linda Yu-Ling, additional, Pope, Rosemary L., additional, Chen, Yani, additional, Rogers, Kai J., additional, Dutta, Nirmal, additional, Toombs, Jason E., additional, Wilson, Mary E., additional, Wilson, Patrick C., additional, Maury, Wendy, additional, Brekken, Rolf A., additional, and Butler, Noah S., additional

Published
2021
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31. 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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34. 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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39. TIM-1 Mediates Dystroglycan-Independent Entry of Lassa Virus

Author

Brouillette, Rachel B., primary, Phillips, Elisabeth K., additional, Patel, Radhika, additional, Mahauad-Fernandez, Wadie, additional, Moller-Tank, Sven, additional, Rogers, Kai J., additional, Dillard, Jacob A., additional, Cooney, Ashley L., additional, Martinez-Sobrido, Luis, additional, Okeoma, Chioma, additional, and Maury, Wendy, additional

Published
2018
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41. TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions

Author

Das, Anshuman, primary, Hirai-Yuki, Asuka, additional, González-López, Olga, additional, Rhein, Bethany, additional, Moller-Tank, Sven, additional, Brouillette, Rachel, additional, Hensley, Lucinda, additional, Misumi, Ichiro, additional, Lovell, William, additional, Cullen, John M., additional, Whitmire, Jason K., additional, Maury, Wendy, additional, and Lemon, Stanley M., additional

Published
2017
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42. Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

Author

Lennemann, Nicholas J., primary, Herbert, Andrew S., additional, Brouillette, Rachel, additional, Rhein, Bethany, additional, Bakken, Russell A., additional, Perschbacher, Katherine J., additional, Cooney, Ashley L., additional, Miller-Hunt, Catherine L., additional, Ten Eyck, Patrick, additional, Biggins, Julia, additional, Olinger, Gene, additional, Dye, John M., additional, and Maury, Wendy, additional

Published
2017
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44. 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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46. Interferon-γ Inhibits Ebola Virus Infection

Author

Rhein, Bethany A., primary, Powers, Linda S., additional, Rogers, Kai, additional, Anantpadma, Manu, additional, Singh, Brajesh K., additional, Sakurai, Yasuteru, additional, Bair, Thomas, additional, Miller-Hunt, Catherine, additional, Sinn, Patrick, additional, Davey, Robert A., additional, Monick, Martha M., additional, and Maury, Wendy, additional

Published
2015
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49. 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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50. Modification of N-Linked Glycan Sites in Viral Glycoproteins.

Author

Lennemann NJ, Corliss L, and Maury W

Subjects
Glycosylation, Protein Processing, Post-Translational, Glycoproteins chemistry, Polysaccharides chemistry
Abstract

Post-translational modification of proteins by the addition of sugar chains, or glycans, is a functionally important hallmark of proteins trafficked through the secretory system. These proteins are termed glycoproteins. Glycans are known to be important for initiating signaling through binding of cell surface receptors, facilitating protein folding, and maintaining protein stability. For pathogens, glycans can also mask vulnerable protein regions from neutralizing antibodies. Thus, there is a need to develop methods to decipher the role of specific glycans attached to proteins in order to understand their biological role. Here, we describe established methods for identifying glycosylated residues and understanding their role in protein synthesis and function using viral glycoproteins as a model., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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