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3. Identification of an immunogenic epitope and protective antibody against the furin cleavage site of SARS-CoV-2

Author

Li, Lili, Gao, Meiling, Li, Jie, Xie, Xuping, Zhao, Hui, Wang, Yanan, Xu, Xin, Zu, Shulong, Chen, Chunfeng, Wan, Dingyi, Duan, Jing, Wang, Jingfeng, Aliyari, Saba R, Gold, Sarah, Zhang, Jicai, Qin, Cheng-Feng, Shi, Pei-Yong, Yang, Heng, and Cheng, Genhong

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Prevention, Biodefense, Infectious Diseases, Pneumonia & Influenza, Vaccine Related, Emerging Infectious Diseases, Immunization, Good Health and Well Being, Animals, Mice, SARS-CoV-2, COVID-19, Furin, Antibody Formation, Epitopes, Leukocytes, Mononuclear, Antibodies, Furin site, Immunogenic epitope, S protein, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the global coronavirus disease 2019 (COVID-19) pandemic, contains a unique, four amino acid (aa) "PRRA" insertion in the spike (S) protein that creates a transmembrane protease serine 2 (TMPRSS2)/furin cleavage site and enhances viral infectivity. More research into immunogenic epitopes and protective antibodies against this SARS-CoV-2 furin cleavage site is needed.MethodsCombining computational and experimental methods, we identified and characterized an immunogenic epitope overlapping the furin cleavage site that detects antibodies in COVID-19 patients and elicits strong antibody responses in immunized mice. We also identified a high-affinity monoclonal antibody from COVID-19 patient peripheral blood mononuclear cells; the antibody directly binds the furin cleavage site and protects against SARS-CoV-2 infection in a mouse model.FindingsThe presence of "PRRA" amino acids in the S protein of SARS-CoV-2 not only creates a furin cleavage site but also generates an immunogenic epitope that elicits an antibody response in COVID-19 patients. An antibody against this epitope protected against SARS-CoV-2 infection in mice.InterpretationThe immunogenic epitope and protective antibody we have identified may augment our strategy in handling COVID-19 epidemic.FundingThe National Natural Science Foundation of China (82102371, 91542201, 81925025, 82073181, and 81802870), the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2021-I2M-1-047 and 2022-I2M-2-004), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2020-PT310-006, 2019XK310002, and 2018TX31001), the National Key Research and Development Project of China (2020YFC0841700), US National Institute of Health (NIH) funds grant AI158154, University of California Los Angeles (UCLA) AI and Charity Treks, and UCLA DGSOM BSCRC COVID-19 Award Program. H.Y. is supported by Natural Science Foundation of Jiangsu Province (BK20211554 andBE2022728).

Published
2023

5. SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients

Author

Pontelli, Marjorie C, Castro, Ítalo A, Martins, Ronaldo B, La Serra, Leonardo, Veras, Flávio P, Nascimento, Daniele C, Silva, Camila M, Cardoso, Ricardo S, Rosales, Roberta, Gomes, Rogério, Lima, Thais M, Souza, Juliano P, Vitti, Brenda C, Caetité, Diego B, de Lima, Mikhael HF, Stumpf, Spencer D, Thompson, Cassandra E, Bloyet, Louis-Marie, Toller-Kawahisa, Juliana E, Giannini, Marcela C, Bonjorno, Letícia P, Lopes, Maria IF, Batah, Sabrina S, Siyuan, Li, Luppino-Assad, Rodrigo, Almeida, Sergio CL, Oliveira, Fabiola R, Benatti, Maíra N, Pontes, Lorena LF, Santana, Rodrigo C, Vilar, Fernando C, Auxiliadora-Martins, Maria, Shi, Pei-Yong, Cunha, Thiago M, Calado, Rodrigo T, Alves-Filho, José C, Zamboni, Dario S, Fabro, Alexandre T, Louzada-Junior, Paulo, Oliveira, Rene DR, Whelan, Sean PJ, Cunha, Fernando Q, and Arruda, Eurico

Abstract

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monocytes, as well as both B and T lymphocytes, were susceptible to SARS-CoV-2 infection in vitro, accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis. In addition, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019 (COVID-19) patients. The rates of SARS-CoV-2-infected monocytes in peripheral blood mononuclear cells from COVID-19 patients increased over time from symptom onset, with SARS-CoV-2-positive monocytes, B cells, and CD4+ T lymphocytes also detected in postmortem lung tissue. These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in COVID-19 patients might have important implications for disease pathogenesis and progression, immune dysfunction, and virus spread within the host.

Published
2022

7. SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode

Author

Goike, Jule, Hsieh, Ching-Lin, Horton, Andrew P., Gardner, Elizabeth C., Zhou, Ling, Bartzoka, Foteini, Wang, Nianshuang, Javanmardi, Kamyab, Herbert, Andrew, Abbassi, Shawn, Xie, Xuping, Xia, Hongjie, Shi, Pei-Yong, Renberg, Rebecca, Segall-Shapiro, Thomas H., Terrace, Cynthia I., Wu, Wesley, Shroff, Raghav, Byrom, Michelle, Ellington, Andrew D., Marcotte, Edward M., Musser, James M., Kuchipudi, Suresh V., Kapur, Vivek, Georgiou, George, Weaver, Scott C., Dye, John M., Boutz, Daniel R., McLellan, Jason S., and Gollihar, Jimmy D.

Published
2023
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10. Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro

Author

Radoshitzky, Sheli R., Iversen, Patrick, Lu, Xianghan, Zou, Jing, Kaptein, Suzanne J. F., Stuthman, Kelly S., Van Tongeren, Sean A., Steffens, Jesse, Gong, Ruoyu, Truong, Hoa, Sapre, Annapurna A., Yang, Huiling, Xie, Xiaodong, Chia, Jia Jun, Song, Zhijuan J., Leventhal, Stacey M., Chan, Josolyn, Shornikov, Alex, Zhang, Xin, Cowfer, David, Yu, Helen, Warren, Travis, Cihlar, Tomas, Porter, Danielle P., Neyts, Johan, Shi, Pei-Yong, Wells, Jay, Bilello, John P., and Feng, Joy Y.

Published
2023
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11. Defining the risk of SARS-CoV-2 variants on immune protection

Author

DeGrace, Marciela M, Ghedin, Elodie, Frieman, Matthew B, Krammer, Florian, Grifoni, Alba, Alisoltani, Arghavan, Alter, Galit, Amara, Rama R, Baric, Ralph S, Barouch, Dan H, Bloom, Jesse D, Bloyet, Louis-Marie, Bonenfant, Gaston, Boon, Adrianus CM, Boritz, Eli A, Bratt, Debbie L, Bricker, Traci L, Brown, Liliana, Buchser, William J, Carreño, Juan Manuel, Cohen-Lavi, Liel, Darling, Tamarand L, Davis-Gardner, Meredith E, Dearlove, Bethany L, Di, Han, Dittmann, Meike, Doria-Rose, Nicole A, Douek, Daniel C, Drosten, Christian, Edara, Venkata-Viswanadh, Ellebedy, Ali, Fabrizio, Thomas P, Ferrari, Guido, Fischer, Will M, Florence, William C, Fouchier, Ron AM, Franks, John, García-Sastre, Adolfo, Godzik, Adam, Gonzalez-Reiche, Ana Silvia, Gordon, Aubree, Haagmans, Bart L, Halfmann, Peter J, Ho, David D, Holbrook, Michael R, Huang, Yaoxing, James, Sarah L, Jaroszewski, Lukasz, Jeevan, Trushar, Johnson, Robert M, Jones, Terry C, Joshi, Astha, Kawaoka, Yoshihiro, Kercher, Lisa, Koopmans, Marion PG, Korber, Bette, Koren, Eilay, Koup, Richard A, LeGresley, Eric B, Lemieux, Jacob E, Liebeskind, Mariel J, Liu, Zhuoming, Livingston, Brandi, Logue, James P, Luo, Yang, McDermott, Adrian B, McElrath, Margaret J, Meliopoulos, Victoria A, Menachery, Vineet D, Montefiori, David C, Mühlemann, Barbara, Munster, Vincent J, Munt, Jenny E, Nair, Manoj S, Netzl, Antonia, Niewiadomska, Anna M, O’Dell, Sijy, Pekosz, Andrew, Perlman, Stanley, Pontelli, Marjorie C, Rockx, Barry, Rolland, Morgane, Rothlauf, Paul W, Sacharen, Sinai, Scheuermann, Richard H, Schmidt, Stephen D, Schotsaert, Michael, Schultz-Cherry, Stacey, Seder, Robert A, Sedova, Mayya, Sette, Alessandro, Shabman, Reed S, Shen, Xiaoying, Shi, Pei-Yong, Shukla, Maulik, Simon, Viviana, Stumpf, Spencer, Sullivan, Nancy J, Thackray, Larissa B, and Theiler, James

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Emerging Infectious Diseases, Pneumonia, Vaccine Related, Pneumonia & Influenza, Infectious Diseases, Biodefense, Immunization, Biotechnology, Prevention, Lung, Prevention of disease and conditions, and promotion of well-being, 2.1 Biological and endogenous factors, 3.4 Vaccines, Aetiology, Infection, Good Health and Well Being, Animals, Biological Evolution, COVID-19, COVID-19 Vaccines, Humans, National Institute of Allergy and Infectious Diseases (U.S.), Pandemics, Pharmacogenomic Variants, SARS-CoV-2, United States, Virulence, General Science & Technology
Abstract

The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases within the National Institutes of Health established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants that could potentially affect the transmission, virulence, and resistance to infection- and vaccine-induced immunity. The SAVE programme is a critical data-generating component of the US Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics, and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models and notable findings facilitated by this collaborative approach and identify future challenges. This programme is a template for the response to rapidly evolving pathogens with pandemic potential by monitoring viral evolution in the human population to identify variants that could reduce the effectiveness of countermeasures.

Published
2022

12. A Zika virus mutation enhances transmission potential and confers escape from protective dengue virus immunity

Author

Regla-Nava, Jose Angel, Wang, Ying-Ting, Fontes-Garfias, Camila R, Liu, Yang, Syed, Thasneem, Susantono, Mercylia, Gonzalez, Andrew, Viramontes, Karla M, Verma, Shailendra Kumar, Kim, Kenneth, Landeras-Bueno, Sara, Huang, Chun-Teng, Prigozhin, Daniil M, Gleeson, Joseph G, Terskikh, Alexey V, Shi, Pei-Yong, and Shresta, Sujan

Subjects
Biological Sciences, Rare Diseases, Vaccine Related, Prevention, Emerging Infectious Diseases, Infectious Diseases, Vector-Borne Diseases, Biodefense, 2.2 Factors relating to the physical environment, Aetiology, Infection, Good Health and Well Being, Animals, Antibodies, Viral, Cross Reactions, Dengue, Dengue Virus, Mice, Mutation, Zika Virus, Zika Virus Infection, CP: Microbiology, Flavivirus evolution, cross-protective immunity, dengue virus, mouse-adapted virus, viral pathogenesis, viral transmission, viral variants, zika virus, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

Zika virus (ZIKV) and dengue virus (DENV) are arthropod-borne pathogenic flaviviruses that co-circulate in many countries. To understand some of the pressures that influence ZIKV evolution, we mimic the natural transmission cycle by repeating serial passaging of ZIKV through cultured mosquito cells and either DENV-naive or DENV-immune mice. Compared with wild-type ZIKV, the strains passaged under both conditions exhibit increased pathogenesis in DENV-immune mice. Application of reverse genetics identifies an isoleucine-to-valine mutation (I39V) in the NS2B proteins of both passaged strains that confers enhanced fitness and escape from pre-existing DENV immunity. Introduction of I39V or I39T, a naturally occurring homologous mutation detected in recent ZIKV isolates, increases the replication of wild-type ZIKV in human neuronal precursor cells and laboratory-raised mosquitoes. Our data indicate that ZIKV strains with enhanced transmissibility and pathogenicity can emerge in DENV-naive or -immune settings, and that NS2B-I39 mutants may represent ZIKV variants of interest.

Published
2022

13. In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains

Author

Chen, Rita E, Winkler, Emma S, Case, James Brett, Aziati, Ishmael D, Bricker, Traci L, Joshi, Astha, Darling, Tamarand L, Ying, Baoling, Errico, John M, Shrihari, Swathi, VanBlargan, Laura A, Xie, Xuping, Gilchuk, Pavlo, Zost, Seth J, Droit, Lindsay, Liu, Zhuoming, Stumpf, Spencer, Wang, David, Handley, Scott A, Stine, W Blaine, Shi, Pei-Yong, Davis-Gardner, Meredith E, Suthar, Mehul S, Knight, Miguel Garcia, Andino, Raul, Chiu, Charles Y, Ellebedy, Ali H, Fremont, Daved H, Whelan, Sean PJ, Crowe, James E, Purcell, Lisa, Corti, Davide, Boon, Adrianus CM, and Diamond, Michael S

Subjects
Infectious Diseases, Pneumonia & Influenza, Immunization, Biodefense, Biotechnology, Lung, Vaccine Related, Pneumonia, Prevention, Emerging Infectious Diseases, Infection, Angiotensin-Converting Enzyme 2, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Chlorocebus aethiops, Female, Humans, Male, Mesocricetus, Mice, Mice, Transgenic, Neutralization Tests, Post-Exposure Prophylaxis, Pre-Exposure Prophylaxis, SARS-CoV-2, Serine Endopeptidases, Spike Glycoprotein, Coronavirus, Vero Cells, General Science & Technology
Abstract

Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-21-3, the in vivo importance of these results remains uncertain. Here we report the in vitro and in vivo activity of a panel of monoclonal antibodies (mAbs), which correspond to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron and Lilly, against SARS-CoV-2 variant viruses. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. Exceptions were LY-CoV555 monotherapy and LY-CoV555 and LY-CoV016 combination therapy, both of which lost all protective activity, and the combination of AbbVie 2B04 and 47D11, which showed a partial loss of activity. When administered after infection, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Therefore, many-but not all-of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2.

Published
2021

15. Zika virus oncolytic activity requires CD8+ T cells and is boosted by immune checkpoint blockade

Author

Nair, Sharmila, Mazzoccoli, Luciano, Jash, Arijita, Govero, Jennifer, Bais, Sachendra S, Hu, Tong, Fontes-Garfias, Camila R, Shan, Chao, Okada, Hideho, Shresta, Sujan, Rich, Jeremy N, Shi, Pei-Yong, Diamond, Michael S, and Chheda, Milan G

Subjects
Cancer, Immunization, Brain Cancer, Rare Diseases, Vaccine Related, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Brain Disorders, Neurosciences, Orphan Drug, Stem Cell Research - Nonembryonic - Human, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Animals, Brain Neoplasms, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Combined Modality Therapy, Female, Glioblastoma, Humans, Immune Checkpoint Inhibitors, Mice, Mice, Inbred C57BL, Neoplasms, Experimental, Oncolytic Virotherapy, Oncolytic Viruses, Tumor Microenvironment, Zika Virus, Brain cancer, Cancer immunotherapy, Immunology, Oncology
Abstract

Glioblastoma multiforme (GBM) is a fatal human cancer in part because GBM stem cells are resistant to therapy and recurrence is inevitable. Previously, we demonstrated Zika virus (ZIKV) targets GBM stem cells and prevents death of mice with gliomas. Here, we evaluated the immunological basis of ZIKV-mediated protection against GBM. Introduction of ZIKV into the brain tumor increased recruitment of CD8+ T and myeloid cells to the tumor microenvironment. CD8+ T cells were required for ZIKV-dependent tumor clearance because survival benefits were lost with CD8+ T cell depletion. Moreover, while anti-PD-1 antibody monotherapy moderately improved tumor survival, when coadministered with ZIKV, survival increased. ZIKV-mediated tumor clearance also resulted in durable protection against syngeneic tumor rechallenge, which also depended on CD8+ T cells. To address safety concerns, we generated an immune-sensitized ZIKV strain, which was effective alone or in combination with immunotherapy. Thus, oncolytic ZIKV treatment can be leveraged by immunotherapies, which may prompt combination treatment paradigms for adult patients with GBM.

Published
2021

18. 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

20. SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry

Author

Kee, John, Thudium, Samuel, Renner, David M., Glastad, Karl, Palozola, Katherine, Zhang, Zhen, Li, Yize, Lan, Yemin, Cesare, Joseph, Poleshko, Andrey, Kiseleva, Anna A., Truitt, Rachel, Cardenas-Diaz, Fabian L., Zhang, Xianwen, Xie, Xuping, Kotton, Darrell N., Alysandratos, Konstantinos D., Epstein, Johnathan A., Shi, Pei-Yong, Yang, Wenli, Morrisey, Edward, Garcia, Benjamin A., Berger, Shelley L., Weiss, Susan R., and Korb, Erica

Published
2022
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22. AT-752 targets multiple sites and activities on the Dengue virus replication enzyme NS5

Author

Feracci, Mikael, Eydoux, Cécilia, Fattorini, Véronique, Lo Bello, Lea, Gauffre, Pierre, Selisko, Barbara, Sutto-Ortiz, Priscila, Shannon, Ashleigh, Xia, Hongjie, Shi, Pei-Yong, Noel, Mathieu, Debart, Françoise, Vasseur, Jean-Jacques, Good, Steve, Lin, Kai, Moussa, Adel, Sommadossi, Jean-Pierre, Chazot, Aurélie, Alvarez, Karine, Guillemot, Jean-Claude, Decroly, Etienne, Ferron, François, and Canard, Bruno

Published
2023
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25. Mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2

Author

Tioni, Mariana F., Jordan, Robert, Pena, Angie Silva, Garg, Aditya, Wu, Danlu, Phan, Shannon I., Weiss, Christopher M., Cheng, Xing, Greenhouse, Jack, Orekov, Tatyana, Valentin, Daniel, Kar, Swagata, Pessaint, Laurent, Andersen, Hanne, Stobart, Christopher C., Bloodworth, Melissa H., Stokes Peebles, R., Liu, Yang, Xie, Xuping, Shi, Pei-Yong, Moore, Martin L., and Tang, Roderick S.

Published
2022
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26. Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines

Author

Wang, Li, Kainulainen, Markus H., Jiang, Nannan, Di, Han, Bonenfant, Gaston, Mills, Lisa, Currier, Michael, Shrivastava-Ranjan, Punya, Calderon, Brenda M., Sheth, Mili, Mann, Brian R., Hossain, Jaber, Lin, Xudong, Lester, Sandra, Pusch, Elizabeth A., Jones, Joyce, Cui, Dan, Chatterjee, Payel, Jenks, M. Harley, Morantz, Esther K., Larson, Gloria P., Hatta, Masato, Harcourt, Jennifer L., Tamin, Azaibi, Li, Yan, Tao, Ying, Zhao, Kun, Lacek, Kristine, Burroughs, Ashley, Wang, Wei, Wilson, Malania, Wong, Terianne, Park, So Hee, Tong, Suxiang, Barnes, John R., Tenforde, Mark W., Self, Wesley H., Shapiro, Nathan I., Exline, Matthew C., Files, D. Clark, Gibbs, Kevin W., Hager, David N., Patel, Manish, Halpin, Alison L., McMullan, Laura K., Lee, Justin S., Xia, Hongjie, Xie, Xuping, Shi, Pei-Yong, Davis, C. Todd, Spiropoulou, Christina F., Thornburg, Natalie J., Oberste, M. Steven, Dugan, Vivien G., Wentworth, David E., and Zhou, Bin

Published
2022
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28. Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth

Author

Ku, Zhiqiang, Xie, Xuping, Lin, Jianqing, Gao, Peng, Wu, Bin, El Sahili, Abbas, Su, Hang, Liu, Yang, Ye, Xiaohua, Tan, Eddie Yongjun, Li, Xin, Fan, Xuejun, Goh, Boon Chong, Xiong, Wei, Boyd, Hannah, Muruato, Antonio E., Deng, Hui, Xia, Hongjie, Zou, Jing, Kalveram, Birte K., Menachery, Vineet D., Zhang, Ningyan, Lescar, Julien, Shi, Pei-Yong, and An, Zhiqiang

Published
2022
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36. High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells.

Author

Gong, Danyang, Zhang, Tian-Hao, Zhao, Dawei, Du, Yushen, Chapa, Travis J, Shi, Yuan, Wang, Laurie, Contreras, Deisy, Zeng, Gang, Shi, Pei-Yong, Wu, Ting-Ting, Arumugaswami, Vaithilingaraja, and Sun, Ren

Subjects
Entomology, Genomics, Protein Structure Aspects, Virology, Vector-Borne Diseases, Infectious Diseases, Prevention, Vaccine Related, Emerging Infectious Diseases, Genetics, Biodefense, Rare Diseases, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Infection
Abstract

Zika virus (ZIKV) infection causes Guillain-Barré syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and is therefore considered one of the major determinants in ZIKV pathogenesis. Here we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library, with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting glycosylation display the most divergence. By characterizing individual mutants, we show that ablation of glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, whereas it either has little impact on ZIKV infection on certain human cells or leads to decreased infection through the entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells.

Published
2018

37. Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae

Author

Muneer, Adil, primary, Xie, Ling, additional, Xie, Xuping, additional, Zhang, Feng, additional, Wrobel, John A., additional, Xiong, Yan, additional, Yu, Xufen, additional, Wang, Charles, additional, Gheorghe, Ciprian, additional, Wu, Ping, additional, Song, Juan, additional, Ming, Guo-Li, additional, Jin, Jian, additional, Song, Hongjun, additional, Shi, Pei-Yong, additional, and Chen, Xian, additional

Published
2024
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40. Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail

Author

Dong, Jinhui, Zost, Seth J., Greaney, Allison J., Starr, Tyler N., Dingens, Adam S., Chen, Elaine C., Chen, Rita E., Case, James Brett, Sutton, Rachel E., Gilchuk, Pavlo, Rodriguez, Jessica, Armstrong, Erica, Gainza, Christopher, Nargi, Rachel S., Binshtein, Elad, Xie, Xuping, Zhang, Xianwen, Shi, Pei-Yong, Logue, James, Weston, Stuart, McGrath, Marisa E., Frieman, Matthew B., Brady, Tyler, Tuffy, Kevin M., Bright, Helen, Loo, Yueh-Ming, McTamney, Patrick M., Esser, Mark T., Carnahan, Robert H., Diamond, Michael S., Bloom, Jesse D., and Crowe, Jr, James E.

Published
2021
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41. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis

Author

Bailey, Adam L., Dmytrenko, Oleksandr, Greenberg, Lina, Bredemeyer, Andrea L., Ma, Pan, Liu, Jing, Penna, Vinay, Winkler, Emma S., Sviben, Sanja, Brooks, Erin, Nair, Ajith P., Heck, Kent A., Rali, Aniket S., Simpson, Leo, Saririan, Mehrdad, Hobohm, Dan, Stump, W. Tom, Fitzpatrick, James A., Xie, Xuping, Zhang, Xianwen, Shi, Pei-Yong, Hinson, J. Travis, Gi, Weng-Tein, Schmidt, Constanze, Leuschner, Florian, Lin, Chieh-Yu, Diamond, Michael S., Greenberg, Michael J., and Lavine, Kory J.

Published
2021
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42. Zika virus has oncolytic activity against glioblastoma stem cells

Author

Zhu, Zhe, Gorman, Matthew J, McKenzie, Lisa D, Chai, Jiani N, Hubert, Christopher G, Prager, Briana C, Fernandez, Estefania, Richner, Justin M, Zhang, Rong, Shan, Chao, Tycksen, Eric, Wang, Xiuxing, Shi, Pei-Yong, Diamond, Michael S, Rich, Jeremy N, and Chheda, Milan G

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Brain Disorders, Stem Cell Research, Orphan Drug, Stem Cell Research - Nonembryonic - Human, Gene Therapy, Stem Cell Research - Nonembryonic - Non-Human, Genetics, Brain Cancer, Neurosciences, West Nile Virus, Cancer, Good Health and Well Being, Animals, Antineoplastic Agents, Alkylating, Brain Neoplasms, Cell Line, Tumor, Cell Proliferation, Chlorocebus aethiops, Combined Modality Therapy, Dacarbazine, Female, Fluorescent Antibody Technique, Glioblastoma, Humans, Mice, Mice, Inbred C57BL, Neoplasms, Experimental, Neoplastic Stem Cells, Oncolytic Virotherapy, Temozolomide, Vero Cells, Zika Virus, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.

Published
2017

43. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses

Author

Turner, Jackson S., O’Halloran, Jane A., Kalaidina, Elizaveta, Kim, Wooseob, Schmitz, Aaron J., Zhou, Julian Q., Lei, Tingting, Thapa, Mahima, Chen, Rita E., Case, James Brett, Amanat, Fatima, Rauseo, Adriana M., Haile, Alem, Xie, Xuping, Klebert, Michael K., Suessen, Teresa, Middleton, William D., Shi, Pei-Yong, Krammer, Florian, Teefey, Sharlene A., Diamond, Michael S., Presti, Rachel M., and Ellebedy, Ali H.

Published
2021
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44. Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants

Author

Ku, Zhiqiang, Xie, Xuping, Hinton, Paul R., Liu, Xinli, Ye, Xiaohua, Muruato, Antonio E., Ng, Dean C., Biswas, Sujit, Zou, Jing, Liu, Yang, Pandya, Deepal, Menachery, Vineet D., Rahman, Sachi, Cao, Yu-An, Deng, Hui, Xiong, Wei, Carlin, Kevin B., Liu, Junquan, Su, Hang, Haanes, Elizabeth J., Keyt, Bruce A., Zhang, Ningyan, Carroll, Stephen F., Shi, Pei-Yong, and An, Zhiqiang

Published
2021
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45. BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans

Author

Sahin, Ugur, Muik, Alexander, Vogler, Isabel, Derhovanessian, Evelyna, Kranz, Lena M., Vormehr, Mathias, Quandt, Jasmin, Bidmon, Nicole, Ulges, Alexander, Baum, Alina, Pascal, Kristen E., Maurus, Daniel, Brachtendorf, Sebastian, Lörks, Verena, Sikorski, Julian, Koch, Peter, Hilker, Rolf, Becker, Dirk, Eller, Ann-Kathrin, Grützner, Jan, Tonigold, Manuel, Boesler, Carsten, Rosenbaum, Corinna, Heesen, Ludwig, Kühnle, Marie-Cristine, Poran, Asaf, Dong, Jesse Z., Luxemburger, Ulrich, Kemmer-Brück, Alexandra, Langer, David, Bexon, Martin, Bolte, Stefanie, Palanche, Tania, Schultz, Armin, Baumann, Sybille, Mahiny, Azita J., Boros, Gábor, Reinholz, Jonas, Szabó, Gábor T., Karikó, Katalin, Shi, Pei-Yong, Fontes-Garfias, Camila, Perez, John L., Cutler, Mark, Cooper, David, Kyratsous, Christos A., Dormitzer, Philip R., Jansen, Kathrin U., and Türeci, Özlem

Published
2021
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46. Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease

Author

Akiyama, Benjamin M, Laurence, Hannah M, Massey, Aaron R, Costantino, David A, Xie, Xuping, Yang, Yujiao, Shi, Pei-Yong, Nix, Jay C, Beckham, J David, and Kieft, Jeffrey S

Subjects
Medical Microbiology, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Biological Sciences, Rare Diseases, Infectious Diseases, Genetics, Emerging Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Animals, Chlorocebus aethiops, Culicidae, Epithelial Cells, Exoribonucleases, Humans, Mice, Mutation, Neurons, Nucleic Acid Conformation, RNA, Untranslated, RNA, Viral, Vero Cells, Zika Virus, Zika Virus Infection, General Science & Technology
Abstract

The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonuclease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonuclease resistance and identifies features that may modulate function in diverse flaviviruses.

Published
2016

47. Susceptibility to SARS-CoV-2 of Cell Lines and Substrates Commonly Used to Diagnose and Isolate Influenza and Other Viruses

Author

Wang, Li, Fan, Xiaoyu, Bonenfant, Gaston, Cui, Dan, Hossain, Jaber, Jiang, Nannan, Larson, Gloria, Currier, Michael, Liddell, Jimma, Wilson, Malania, Tamin, Azaibi, Harcourt, Jennifer, Ciomperlik-Patton, Jessica, Pang, Hong, Dybdahl-Sissoko, Naomi, Campagnoli, Ray, Shi, Pei-Yong, Barnes, John, Thornburg, Natalie J., Wentworth, David E., and Zhou, Bin

Subjects
Cell lines -- Research, Influenza viruses -- Research, Disease susceptibility -- Research, Virus research, Health
Abstract

Coronavirus disease (COVID-19) has resulted in >70 million laboratory-confirmed cases and >1.6 million deaths in Isolating and propagating viruses from clinical specimens in cell cultures or embryonated chicken eggs is [...]

Published
2021
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48. BNT162b vaccines protect rhesus macaques from SARS-CoV-2

Author

Vogel, Annette B., Kanevsky, Isis, Che, Ye, Swanson, Kena A., Muik, Alexander, Vormehr, Mathias, Kranz, Lena M., Walzer, Kerstin C., Hein, Stephanie, Güler, Alptekin, Loschko, Jakob, Maddur, Mohan S., Ota-Setlik, Ayuko, Tompkins, Kristin, Cole, Journey, Lui, Bonny G., Ziegenhals, Thomas, Plaschke, Arianne, Eisel, David, Dany, Sarah C., Fesser, Stephanie, Erbar, Stephanie, Bates, Ferdia, Schneider, Diana, Jesionek, Bernadette, Sänger, Bianca, Wallisch, Ann-Kathrin, Feuchter, Yvonne, Junginger, Hanna, Krumm, Stefanie A., Heinen, André P., Adams-Quack, Petra, Schlereth, Julia, Schille, Stefan, Kröner, Christoph, de la Caridad Güimil Garcia, Ramón, Hiller, Thomas, Fischer, Leyla, Sellers, Rani S., Choudhary, Shambhunath, Gonzalez, Olga, Vascotto, Fulvia, Gutman, Matthew R., Fontenot, Jane A., Hall-Ursone, Shannan, Brasky, Kathleen, Griffor, Matthew C., Han, Seungil, Su, Andreas A. H., Lees, Joshua A., Nedoma, Nicole L., Mashalidis, Ellene H., Sahasrabudhe, Parag V., Tan, Charles Y., Pavliakova, Danka, Singh, Guy, Fontes-Garfias, Camila, Pride, Michael, Scully, Ingrid L., Ciolino, Tara, Obregon, Jennifer, Gazi, Michal, Carrion, Jr, Ricardo, Alfson, Kendra J., Kalina, Warren V., Kaushal, Deepak, Shi, Pei-Yong, Klamp, Thorsten, Rosenbaum, Corinna, Kuhn, Andreas N., Türeci, Özlem, Dormitzer, Philip R., Jansen, Kathrin U., and Sahin, Ugur

Published
2021
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49. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

Author

Chen, Rita E., Zhang, Xianwen, Case, James Brett, Winkler, Emma S., Liu, Yang, VanBlargan, Laura A., Liu, Jianying, Errico, John M., Xie, Xuping, Suryadevara, Naveenchandra, Gilchuk, Pavlo, Zost, Seth J., Tahan, Stephen, Droit, Lindsay, Turner, Jackson S., Kim, Wooseob, Schmitz, Aaron J., Thapa, Mahima, Wang, David, Boon, Adrianus C. M., Presti, Rachel M., O’Halloran, Jane A., Kim, Alfred H. J., Deepak, Parakkal, Pinto, Dora, Fremont, Daved H., Crowe, Jr, James E., Corti, Davide, Virgin, Herbert W., Ellebedy, Ali H., Shi, Pei-Yong, and Diamond, Michael S.

Published
2021
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50. Spike mutation D614G alters SARS-CoV-2 fitness

Author

Plante, Jessica A., Liu, Yang, Liu, Jianying, Xia, Hongjie, Johnson, Bryan A., Lokugamage, Kumari G., Zhang, Xianwen, Muruato, Antonio E., Zou, Jing, Fontes-Garfias, Camila R., Mirchandani, Divya, Scharton, Dionna, Bilello, John P., Ku, Zhiqiang, An, Zhiqiang, Kalveram, Birte, Freiberg, Alexander N., Menachery, Vineet D., Xie, Xuping, Plante, Kenneth S., Weaver, Scott C., and Shi, Pei-Yong

Published
2021
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