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Study of Camelpox Virus Pathogenesis in Athymic Nude Mice

Camelpox virus (CMLV) is the closest known orthopoxvirus genetically related to variola virus. So far, CMLV was restricted to camelids but, recently, three human cases of camelpox have been described in India, highlighting the need to pursue research on its pathogenesis, which has been hampered by t...

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Autores principales: Duraffour, Sophie, Matthys, Patrick, van den Oord, Joost J., De Schutter, Tim, Mitera, Tania, Snoeck, Robert, Andrei, Graciela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125194/
https://www.ncbi.nlm.nih.gov/pubmed/21738709
http://dx.doi.org/10.1371/journal.pone.0021561
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author Duraffour, Sophie
Matthys, Patrick
van den Oord, Joost J.
De Schutter, Tim
Mitera, Tania
Snoeck, Robert
Andrei, Graciela
author_facet Duraffour, Sophie
Matthys, Patrick
van den Oord, Joost J.
De Schutter, Tim
Mitera, Tania
Snoeck, Robert
Andrei, Graciela
author_sort Duraffour, Sophie
collection PubMed
description Camelpox virus (CMLV) is the closest known orthopoxvirus genetically related to variola virus. So far, CMLV was restricted to camelids but, recently, three human cases of camelpox have been described in India, highlighting the need to pursue research on its pathogenesis, which has been hampered by the lack of small animal models. Here, we confirm that NMRI immunocompetent mice are resistant to intranasal (i.n.) CMLV infection. However, we demonstrate that CMLV induced a severe disease following i.n. challenge of athymic nude mice, which was accompanied with a failure in gaining weight, leading to euthanasia of the animals. On the other hand, intracutaneous (i.c.) infection resulted in disease development without impacting the body weight evolution. CMLV replication in tissues and body fluids was confirmed in the two models. We further analyzed innate immune and B cell responses induced in the spleen and draining lymph nodes after exposure to CMLV. In both models, strong increases in CD11b(+)F4/80(+) macrophages were seen in the spleen, while neutrophils, NK and B cell responses varied between the routes of infection. In the lymph nodes, the magnitude of CD11c(+)CD8α(+) lymphoid and CD11c(+)CD11b(+) myeloid dendritic cell responses increased in i.n. challenged animals. Analysis of cytokine profiles revealed significant increases of interleukin (IL)-6 and IL-18 in the sera of infected animals, while those of other cytokines were similar to uninfected controls. The efficacy of two antivirals (cidofovir or HPMPC, and its 2, 6-diaminopurine analog) was evaluated in both models. HPMPC was the most effective molecule affording 100% protection from morbidity. It appeared that both treatments did not affect immune cell responses or cytokine expression. In conclusion, we demonstrated that immunodeficient mice are permissive for CMLV propagation. These results provide a basis for studying the pathogenesis of CMLV, as well as for evaluating potential antiviral therapies in an immunodeficiency context.
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spelling pubmed-31251942011-07-07 Study of Camelpox Virus Pathogenesis in Athymic Nude Mice Duraffour, Sophie Matthys, Patrick van den Oord, Joost J. De Schutter, Tim Mitera, Tania Snoeck, Robert Andrei, Graciela PLoS One Research Article Camelpox virus (CMLV) is the closest known orthopoxvirus genetically related to variola virus. So far, CMLV was restricted to camelids but, recently, three human cases of camelpox have been described in India, highlighting the need to pursue research on its pathogenesis, which has been hampered by the lack of small animal models. Here, we confirm that NMRI immunocompetent mice are resistant to intranasal (i.n.) CMLV infection. However, we demonstrate that CMLV induced a severe disease following i.n. challenge of athymic nude mice, which was accompanied with a failure in gaining weight, leading to euthanasia of the animals. On the other hand, intracutaneous (i.c.) infection resulted in disease development without impacting the body weight evolution. CMLV replication in tissues and body fluids was confirmed in the two models. We further analyzed innate immune and B cell responses induced in the spleen and draining lymph nodes after exposure to CMLV. In both models, strong increases in CD11b(+)F4/80(+) macrophages were seen in the spleen, while neutrophils, NK and B cell responses varied between the routes of infection. In the lymph nodes, the magnitude of CD11c(+)CD8α(+) lymphoid and CD11c(+)CD11b(+) myeloid dendritic cell responses increased in i.n. challenged animals. Analysis of cytokine profiles revealed significant increases of interleukin (IL)-6 and IL-18 in the sera of infected animals, while those of other cytokines were similar to uninfected controls. The efficacy of two antivirals (cidofovir or HPMPC, and its 2, 6-diaminopurine analog) was evaluated in both models. HPMPC was the most effective molecule affording 100% protection from morbidity. It appeared that both treatments did not affect immune cell responses or cytokine expression. In conclusion, we demonstrated that immunodeficient mice are permissive for CMLV propagation. These results provide a basis for studying the pathogenesis of CMLV, as well as for evaluating potential antiviral therapies in an immunodeficiency context. Public Library of Science 2011-06-28 /pmc/articles/PMC3125194/ /pubmed/21738709 http://dx.doi.org/10.1371/journal.pone.0021561 Text en Duraffour et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Duraffour, Sophie
Matthys, Patrick
van den Oord, Joost J.
De Schutter, Tim
Mitera, Tania
Snoeck, Robert
Andrei, Graciela
Study of Camelpox Virus Pathogenesis in Athymic Nude Mice
title Study of Camelpox Virus Pathogenesis in Athymic Nude Mice
title_full Study of Camelpox Virus Pathogenesis in Athymic Nude Mice
title_fullStr Study of Camelpox Virus Pathogenesis in Athymic Nude Mice
title_full_unstemmed Study of Camelpox Virus Pathogenesis in Athymic Nude Mice
title_short Study of Camelpox Virus Pathogenesis in Athymic Nude Mice
title_sort study of camelpox virus pathogenesis in athymic nude mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125194/
https://www.ncbi.nlm.nih.gov/pubmed/21738709
http://dx.doi.org/10.1371/journal.pone.0021561
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