Engineering attenuated virulence of a Theileria annulata-infected macrophage.
Live attenuated vaccines are used to combat tropical theileriosis in North Africa, the Middle East, India, and China. The attenuation process is empirical and occurs only after many months, sometimes years, of in vitro culture of virulent clinical isolates. During this extensive culturing, attenuate...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC4222746?pdf=render |
| _version_ | 1818266246070665216 |
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| author | Nadia Echebli Moez Mhadhbi Marie Chaussepied Catherine Vayssettes James P Di Santo Mohamed Aziz Darghouth Gordon Langsley |
| author_facet | Nadia Echebli Moez Mhadhbi Marie Chaussepied Catherine Vayssettes James P Di Santo Mohamed Aziz Darghouth Gordon Langsley |
| author_sort | Nadia Echebli |
| collection | DOAJ |
| description | Live attenuated vaccines are used to combat tropical theileriosis in North Africa, the Middle East, India, and China. The attenuation process is empirical and occurs only after many months, sometimes years, of in vitro culture of virulent clinical isolates. During this extensive culturing, attenuated lines lose their vaccine potential. To circumvent this we engineered the rapid ablation of the host cell transcription factor c-Jun, and within only 3 weeks the line engineered for loss of c-Jun activation displayed in vitro correlates of attenuation such as loss of adhesion, reduced MMP9 gelatinase activity, and diminished capacity to traverse Matrigel. Specific ablation of a single infected host cell virulence trait (c-Jun) induced a complete failure of Theileria annulata-transformed macrophages to disseminate, whereas virulent macrophages disseminated to the kidneys, spleen, and lungs of Rag2/γC mice. Thus, in this heterologous mouse model loss of c-Jun expression led to ablation of dissemination of T. annulata-infected and transformed macrophages. The generation of Theileria-infected macrophages genetically engineered for ablation of a specific host cell virulence trait now makes possible experimental vaccination of calves to address how loss of macrophage dissemination impacts the disease pathology of tropical theileriosis. |
| first_indexed | 2024-12-12T20:03:39Z |
| format | Article |
| id | doaj.art-4416be7d040741b780ff14a4b56677ab |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-12T20:03:39Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-4416be7d040741b780ff14a4b56677ab2022-12-22T00:13:42ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352014-01-01811e318310.1371/journal.pntd.0003183Engineering attenuated virulence of a Theileria annulata-infected macrophage.Nadia EchebliMoez MhadhbiMarie ChaussepiedCatherine VayssettesJames P Di SantoMohamed Aziz DarghouthGordon LangsleyLive attenuated vaccines are used to combat tropical theileriosis in North Africa, the Middle East, India, and China. The attenuation process is empirical and occurs only after many months, sometimes years, of in vitro culture of virulent clinical isolates. During this extensive culturing, attenuated lines lose their vaccine potential. To circumvent this we engineered the rapid ablation of the host cell transcription factor c-Jun, and within only 3 weeks the line engineered for loss of c-Jun activation displayed in vitro correlates of attenuation such as loss of adhesion, reduced MMP9 gelatinase activity, and diminished capacity to traverse Matrigel. Specific ablation of a single infected host cell virulence trait (c-Jun) induced a complete failure of Theileria annulata-transformed macrophages to disseminate, whereas virulent macrophages disseminated to the kidneys, spleen, and lungs of Rag2/γC mice. Thus, in this heterologous mouse model loss of c-Jun expression led to ablation of dissemination of T. annulata-infected and transformed macrophages. The generation of Theileria-infected macrophages genetically engineered for ablation of a specific host cell virulence trait now makes possible experimental vaccination of calves to address how loss of macrophage dissemination impacts the disease pathology of tropical theileriosis.http://europepmc.org/articles/PMC4222746?pdf=render |
| spellingShingle | Nadia Echebli Moez Mhadhbi Marie Chaussepied Catherine Vayssettes James P Di Santo Mohamed Aziz Darghouth Gordon Langsley Engineering attenuated virulence of a Theileria annulata-infected macrophage. PLoS Neglected Tropical Diseases |
| title | Engineering attenuated virulence of a Theileria annulata-infected macrophage. |
| title_full | Engineering attenuated virulence of a Theileria annulata-infected macrophage. |
| title_fullStr | Engineering attenuated virulence of a Theileria annulata-infected macrophage. |
| title_full_unstemmed | Engineering attenuated virulence of a Theileria annulata-infected macrophage. |
| title_short | Engineering attenuated virulence of a Theileria annulata-infected macrophage. |
| title_sort | engineering attenuated virulence of a theileria annulata infected macrophage |
| url | http://europepmc.org/articles/PMC4222746?pdf=render |
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