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24 results on '"Sirohi, Devika"'

3. prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis

Author

A. Dowd, Kimberly, primary, Sirohi, Devika, additional, D. Speer, Scott, additional, VanBlargan, Laura A., additional, Chen, Rita E., additional, Mukherjee, Swati, additional, Whitener, Bradley M., additional, Govero, Jennifer, additional, Aleshnick, Maya, additional, Larman, Bridget, additional, Sukupolvi-Petty, Soila, additional, Sevvana, Madhumati, additional, Miller, Andrew S., additional, Klose, Thomas, additional, Zheng, Aihua, additional, Koenig, Scott, additional, Kielian, Margaret, additional, Kuhn, Richard J., additional, Diamond, Michael S., additional, and Pierson, Theodore C., additional

Published
2023
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5. prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis.

Author

Dowd, Kimberly A., Sirohi, Devika, Speer, Scott D., VanBlargan, Laura A., Chen, Rita E., Mukherjee, Swati, Whitener, Bradley M., Govero, Jennifer, Aleshnick, Maya, Larman, Bridget, Sukupolvi-Petty, Soila, Sevvana, Madhumati, Miller, Andrew S., Klose, Thomas, Aihua Zheng, Koenig, Scott, Kielian, Margaret, Kuhn, Richard J., Diamond, Michael S., and Pierson, Theodore C.

Subjects
*DENGUE viruses, *VIRION, *CYTOSKELETAL proteins, *MONOCLONAL antibodies, *IMMUNOGLOBULINS
Abstract

Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis during primary infection is unknown. To investigate this question, we characterized the functional properties of newly-generated dengue virus (DENV) prM-reactive monoclonal antibodies (mAbs) in vitro and using a mouse model of DENV disease. Anti-prM mAbs neutralized DENV infection in a virion maturation state--dependent manner. Alanine scanning mutagenesis and cryoelectron microscopy of anti-prM mAbs in complex with immature DENV defined two modes of attachment to a single antigenic site. In vivo, passive transfer of intact anti-prM mAbs resulted in an antibody-dependent enhancement of disease. However, protection against DENV- induced lethality was observed when the transferred mAbs were genetically modified to inhibit their ability to interact with Fcy receptors. These data establish that in addition to mature forms of the virus, partially mature infectious prM+ virions can also contribute to pathogenesis during primary DENV infections. [ABSTRACT FROM AUTHOR]

Published
2023
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7. Chloropyridinyl Esters of Nonsteroidal Anti-Inflammatory Agents and Related Derivatives as Potent SARS-CoV-2 3CL Protease Inhibitors

Author

Ghosh, Arun K., primary, Shahabi, Dana, additional, Yadav, Monika, additional, Kovela, Satish, additional, Anson, Brandon J., additional, Lendy, Emma K., additional, Bonham, Connie, additional, Sirohi, Devika, additional, Brito-Sierra, Carlos A., additional, Hattori, Shin-ichiro, additional, Kuhn, Richard, additional, Mitsuya, Hiroaki, additional, and Mesecar, Andrew D., additional

Published
2021
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8. Complementary use of mass spectrometry and cryo-electron microscopy to assess the maturity of live attenuated dengue vaccine viruses

Author

Trauchessec, Mathieu, primary, Lambert, Olivier, additional, Bonnafous, Pierre, additional, Berard, Yves, additional, Barriere, Fabienne, additional, Huillet, Celine, additional, Marco, Sergio, additional, Sirohi, Devika, additional, Hedrick, Victoria, additional, Kuhn, Richard, additional, Guy, Bruno, additional, Ronzon, Frederic, additional, and Manin, Catherine, additional

Published
2019
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15. The cryoEM structures of immature and mature Zika virus and of mature Zika virus complexed with a human monoclonal antibody

Author

Sirohi, Devika, primary, Chen, Zhenguo, additional, Sun, Lei, additional, Klose, Thomas, additional, Pierson, Theodore C., additional, Rossmann, Michael G., additional, Kuhn, Richard J., additional, Prasad, Vidya Mangala, additional, Miller, Andrew, additional, Buda, Geeta, additional, Hasan, S. Saif, additional, Sapparapu, Gopal, additional, Fernandez, Estefania, additional, Long, Feng, additional, Fokine, Andrey, additional, Porta, Jason C., additional, Jiang, Wen, additional, Diamond, Michael S., additional, and Crowe, James E., additional

Published
2017
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23. Impact of Dengue Virus Infection on Global Metabolic Alterations in the Aedes aegyptiMosquito Vector

Author

Chotiwan, Nunya, Sanchez-Vargus, Irma, Grabowski, Jeffrey M., Hopf-jannasch, Amber, Hedrick, Victoria, Gough, Erik, Nakayasu, Ernesto, Sirohi, Devika, Hill, Catherine A., Kuhn, Richard J., and Perera, Rushika

Abstract

Aedes aegyptimosquitoes are the primary vectors transmitting dengue virus (DENV), one of the most aggressive re-emerging pathogens worldwide causing more than 390 million infections per year. The spread of the virus is greatly dependent upon successful replication within both the human host and mosquito vector. Much effort has been placed in understanding the dynamics of virus transmission and replication in both organisms, but little is known about the global impact of DENV on metabolic pathways. Previous studies have demonstrated perturbations in human and Aedes albopictuscellular metabolic environments during DENV infection. Some of these perturbations include increasing the production of membranous lipids that had the capability to induce membrane curvature and permeability, as well as visibly altering both human and mosquito intracellular membrane architecture to support DENV replication. In this study, we have explored metabolic changes in Aedes aegyptimidgut and salivary glands upon DENV (serotype 2) infection. We have found several significant fluctuations in the lipid and metabolite repertoire from infected tissues compared to uninfected controls, including differential expression of molecules that function as membrane building blocks, bioactive messengers, energy storage and intermediates in lipid biosynthesis and lipolysis pathways. These results and their relevance to dengue virus infection of its mosquito vector will be discussed.

Published
2015
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24. Zika Virus Can Strongly Infect and Disrupt Secondary Organizers in the Ventricular Zone of the Embryonic Chicken Brain

Abstract

Zika virus (ZIKV) is associated with severe neurodeve- lopmental impairments in human fetuses, including microencephaly. Previous reports examining neural progenitor tropism of ZIKV in organoid and animal models did not address whether the virus infects all neural progenitors uniformly. To explore this, ZIKV was injected into the neural tube of 2-day-old chicken embryos, resulting in nonuniform periventricular infec- tion 3 days later. Recurrent foci of intense infection were present at specific signaling centers that influ- ence neuroepithelial patterning at a distance through secretion of morphogens. ZIKV infection reduced transcript levels for 3 morphogens, SHH, BMP7, and FGF8 expressed at the midbrain basal plate, hypotha- lamic floor plate, and isthmus, respectively. Levels of Patched1, a SHH-pathway downstream gene, were also reduced, and a SHH-dependent cell popula- tion in the ventral midbrain was shifted in position. Thus, the diminishment of signaling centers through ZIKV-mediated apoptosis may yield broader, non- cell-autonomous changes in brain patterning.

Published
2018

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