Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus
Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188545/ |
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pubmed-3188545 |
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pubmed-31885452011-10-13 Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus Wahl-Jensen, Victoria Cann, Jennifer A. Rubins, Kathleen H. Huggins, John W. Fisher, Robert W. Johnson, Anthony J. de Kok-Mercado, Fabian Larsen, Thomas Raymond, Jo Lynne Hensley, Lisa E. Jahrling, Peter B. Research Article Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions. Public Library of Science 2011-10-06 /pmc/articles/PMC3188545/ /pubmed/21998632 http://dx.doi.org/10.1371/journal.pone.0024832 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Wahl-Jensen, Victoria Cann, Jennifer A. Rubins, Kathleen H. Huggins, John W. Fisher, Robert W. Johnson, Anthony J. de Kok-Mercado, Fabian Larsen, Thomas Raymond, Jo Lynne Hensley, Lisa E. Jahrling, Peter B. |
| spellingShingle |
Wahl-Jensen, Victoria Cann, Jennifer A. Rubins, Kathleen H. Huggins, John W. Fisher, Robert W. Johnson, Anthony J. de Kok-Mercado, Fabian Larsen, Thomas Raymond, Jo Lynne Hensley, Lisa E. Jahrling, Peter B. Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus |
| author_facet |
Wahl-Jensen, Victoria Cann, Jennifer A. Rubins, Kathleen H. Huggins, John W. Fisher, Robert W. Johnson, Anthony J. de Kok-Mercado, Fabian Larsen, Thomas Raymond, Jo Lynne Hensley, Lisa E. Jahrling, Peter B. |
| author_sort |
Wahl-Jensen, Victoria |
| title |
Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus |
| title_short |
Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus |
| title_full |
Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus |
| title_fullStr |
Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus |
| title_full_unstemmed |
Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus |
| title_sort |
progression of pathogenic events in cynomolgus macaques infected with variola virus |
| description |
Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions. |
| publisher |
Public Library of Science |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188545/ |
| _version_ |
1611479470559985664 |