Characterization of Lethal Zika Virus Infection in AG129 Mice.
BACKGROUND:Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause mic...
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ftdoajarticles:oai:doaj.org/article:6dac1ef8ac8b4bf7bdae5d90ecb016e4 2023-05-15T15:13:37+02:00 Characterization of Lethal Zika Virus Infection in AG129 Mice. Matthew T Aliota Elizabeth A Caine Emma C Walker Katrina E Larkin Erwin Camacho Jorge E Osorio 2016-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004682 https://doaj.org/article/6dac1ef8ac8b4bf7bdae5d90ecb016e4 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4836712?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004682 https://doaj.org/article/6dac1ef8ac8b4bf7bdae5d90ecb016e4 PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004682 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004682 2022-12-31T13:27:19Z BACKGROUND:Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage. METHODOLOGY/PRINCIPAL FINDINGS:Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice), we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice. CONCLUSIONS/SIGNIFICANCE:Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 4 e0004682 |
institution |
Open Polar |
collection |
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 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Matthew T Aliota Elizabeth A Caine Emma C Walker Katrina E Larkin Erwin Camacho Jorge E Osorio Characterization of Lethal Zika Virus Infection in AG129 Mice. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage. METHODOLOGY/PRINCIPAL FINDINGS:Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice), we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice. CONCLUSIONS/SIGNIFICANCE:Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing. |
format |
Article in Journal/Newspaper |
author |
Matthew T Aliota Elizabeth A Caine Emma C Walker Katrina E Larkin Erwin Camacho Jorge E Osorio |
author_facet |
Matthew T Aliota Elizabeth A Caine Emma C Walker Katrina E Larkin Erwin Camacho Jorge E Osorio |
author_sort |
Matthew T Aliota |
title |
Characterization of Lethal Zika Virus Infection in AG129 Mice. |
title_short |
Characterization of Lethal Zika Virus Infection in AG129 Mice. |
title_full |
Characterization of Lethal Zika Virus Infection in AG129 Mice. |
title_fullStr |
Characterization of Lethal Zika Virus Infection in AG129 Mice. |
title_full_unstemmed |
Characterization of Lethal Zika Virus Infection in AG129 Mice. |
title_sort |
characterization of lethal zika virus infection in ag129 mice. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004682 https://doaj.org/article/6dac1ef8ac8b4bf7bdae5d90ecb016e4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004682 (2016) |
op_relation |
http://europepmc.org/articles/PMC4836712?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004682 https://doaj.org/article/6dac1ef8ac8b4bf7bdae5d90ecb016e4 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004682 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
10 |
container_issue |
4 |
container_start_page |
e0004682 |
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