A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice.
Dengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a sev...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0125476&type=printable |
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| author | Gregg N Milligan Vanessa V Sarathy Ernesto Infante Li Li Gerald A Campbell P Robert Beatty Eva Harris Alan D T Barrett Nigel Bourne |
| author_facet | Gregg N Milligan Vanessa V Sarathy Ernesto Infante Li Li Gerald A Campbell P Robert Beatty Eva Harris Alan D T Barrett Nigel Bourne |
| author_sort | Gregg N Milligan |
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| description | Dengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a severe life-threatening disease. Infection with one serotype of DENV results in life-long homotypic immunity but only short term heterotypic protection. There are no licensed vaccines or antivirals for dengue due in part to difficulty in developing small animal models that mimic the systemic disease seen in humans. Consequently, an important advance was the description of models of DENV-2 infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor signaling) that resemble human disease. However, the need for well characterized models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4. Following intraperitoneal challenge, animals experience a rapidly progressive lethal infection without developing neurologic clinical signs of disease. High virus titers are seen in multiple visceral tissues including the liver, spleen and large intestine, and the infected animals develop vascular leakage and thrombocytopenia, hallmarks of human dengue. Taken together, our studies demonstrate that this model is an important addition to the field of dengue research particularly in understanding similarities and differences in the pathologic basis of the disease caused by different DENV serotypes and in determining comparative efficacy of putative vaccines and antivirals. |
| format | Article |
| id | doaj-art-ecbc5b4f2c6b4fecbcf52264b3055192 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-ecbc5b4f2c6b4fecbcf52264b30551922025-08-20T02:34:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012547610.1371/journal.pone.0125476A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice.Gregg N MilliganVanessa V SarathyErnesto InfanteLi LiGerald A CampbellP Robert BeattyEva HarrisAlan D T BarrettNigel BourneDengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a severe life-threatening disease. Infection with one serotype of DENV results in life-long homotypic immunity but only short term heterotypic protection. There are no licensed vaccines or antivirals for dengue due in part to difficulty in developing small animal models that mimic the systemic disease seen in humans. Consequently, an important advance was the description of models of DENV-2 infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor signaling) that resemble human disease. However, the need for well characterized models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4. Following intraperitoneal challenge, animals experience a rapidly progressive lethal infection without developing neurologic clinical signs of disease. High virus titers are seen in multiple visceral tissues including the liver, spleen and large intestine, and the infected animals develop vascular leakage and thrombocytopenia, hallmarks of human dengue. Taken together, our studies demonstrate that this model is an important addition to the field of dengue research particularly in understanding similarities and differences in the pathologic basis of the disease caused by different DENV serotypes and in determining comparative efficacy of putative vaccines and antivirals.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0125476&type=printable |
| spellingShingle | Gregg N Milligan Vanessa V Sarathy Ernesto Infante Li Li Gerald A Campbell P Robert Beatty Eva Harris Alan D T Barrett Nigel Bourne A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice. PLoS ONE |
| title | A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice. |
| title_full | A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice. |
| title_fullStr | A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice. |
| title_full_unstemmed | A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice. |
| title_short | A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice. |
| title_sort | dengue virus type 4 model of disseminated lethal infection in ag129 mice |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0125476&type=printable |
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