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...
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ftdoajarticles:oai:doaj.org/article:4416be7d040741b780ff14a4b56677ab 2023-05-15T15:07:27+02:00 Engineering attenuated virulence of a Theileria annulata-infected macrophage. Nadia Echebli Moez Mhadhbi Marie Chaussepied Catherine Vayssettes James P Di Santo Mohamed Aziz Darghouth Gordon Langsley 2014-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003183 https://doaj.org/article/4416be7d040741b780ff14a4b56677ab EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4222746?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003183 https://doaj.org/article/4416be7d040741b780ff14a4b56677ab PLoS Neglected Tropical Diseases, Vol 8, Iss 11, p e3183 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003183 2022-12-31T03:22:27Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 11 e3183 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 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. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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. |
format |
Article in Journal/Newspaper |
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 |
title |
Engineering attenuated virulence of a Theileria annulata-infected macrophage. |
title_short |
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_sort |
engineering attenuated virulence of a theileria annulata-infected macrophage. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003183 https://doaj.org/article/4416be7d040741b780ff14a4b56677ab |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 11, p e3183 (2014) |
op_relation |
http://europepmc.org/articles/PMC4222746?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003183 https://doaj.org/article/4416be7d040741b780ff14a4b56677ab |
op_doi |
https://doi.org/10.1371/journal.pntd.0003183 |
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PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
11 |
container_start_page |
e3183 |
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