Recombinant Lloviu virus as a tool to study viral replication and host responses
| Autor: | Hume, Adam J., Heiden, Baylee, Olejnik, Judith, Suder, Ellen L., Ross, Stephen, Scoon, Whitney A., Bullitt, Esther, Ericsson, Maria, White, Mitchell R., Turcinovic, Jacquelyn, Tran, T N Thao, Hekman, Ryan M., Kaserman, Joseph E., Huang, Jessie, Alysandratos, Konstantinos-Dionysios, Toth, Gabor E., Jakab, Ferenc, Kotton, Darrell N., Wilson, Andrew A., Emili, Andrew, Thiel, Volker, Connor, John H., Kemenesi, Gabor, Cifuentes, Daniel, Mühlberger, Elke, Spiropoulou, Christina F. |
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| Rok vydání: | 2022 |
| Předmět: |
QH301-705.5
viruses Induced Pluripotent Stem Cells Immunology 610 Medicine & health Genome Viral Virus Replication Microbiology Cell Line Virology Chlorocebus aethiops Filoviridae Infections Genetics Animals Humans Biology (General) Vero Cells Molecular Biology Inclusion Bodies Host Microbial Interactions 630 Agriculture Macrophages Genetic Complementation Test Virion Hemorrhagic Fever Ebola RC581-607 Ebolavirus Filoviridae Reverse Genetics RNA Viral 570 Life sciences biology 590 Animals (Zoology) Parasitology Immunologic diseases. Allergy |
| Zdroj: | PLoS Pathogens, Vol 18, Iss 2, p e1010268 (2022) Hume, Adam J.; Heiden, Baylee; Olejnik, Judith; Suder, Ellen L.; Ross, Stephen; Scoon, Whitney A.; Bullitt, Esther; Ericsson, Maria; White, Mitchell R.; Turcinovic, Jacquelyn; Tran, T N Thao; Hekman, Ryan M.; Kaserman, Joseph E.; Huang, Jessie; Alysandratos, Konstantinos-Dionysios; Toth, Gabor E.; Jakab, Ferenc; Kotton, Darrell N.; Wilson, Andrew A.; Emili, Andrew; ... (2022). Recombinant Lloviu virus as a tool to study viral replication and host responses. PLoS pathogens, 18(2), e1010268. Public Library of Science 10.1371/journal.ppat.1010268 |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1010268 |
| Popis: | Next generation sequencing has revealed the presence of numerous RNA viruses in animal reservoir hosts, including many closely related to known human pathogens. Despite their zoonotic potential, most of these viruses remain understudied due to not yet being cultured. While reverse genetic systems can facilitate virus rescue, this is often hindered by missing viral genome ends. A prime example is Lloviu virus (LLOV), an uncultured filovirus that is closely related to the highly pathogenic Ebola virus. Using minigenome systems, we complemented the missing LLOV genomic ends and identified cis-acting elements required for LLOV replication that were lacking in the published sequence. We leveraged these data to generate recombinant full-length LLOV clones and rescue infectious virus. Similar to other filoviruses, recombinant LLOV (rLLOV) forms filamentous virions and induces the formation of characteristic inclusions in the cytoplasm of the infected cells, as shown by electron microscopy. Known target cells of Ebola virus, including macrophages and hepatocytes, are permissive to rLLOV infection, suggesting that humans could be potential hosts. However, inflammatory responses in human macrophages, a hallmark of Ebola virus disease, are not induced by rLLOV. Additional tropism testing identified pneumocytes as capable of robust rLLOV and Ebola virus infection. We also used rLLOV to test antivirals targeting multiple facets of the replication cycle. Rescue of uncultured viruses of pathogenic concern represents a valuable tool in our arsenal for pandemic preparedness. |
| Databáze: | OpenAIRE |
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