Dengue transmission model by means of viremic adult immuno-competent mouse

Abstract Background Dengue virus infection manifests in three distinct forms in humans: dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Infection with the virus is a fatal disease; no vaccine is available and prevention depends on interruption of the chain of transmission. The stu...

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Main Authors: Lucky Ronald Runtuwene, Eiji Konishi, Atsushi Yamanaka, Yoshihiro Makino, Yutaka Suzuki, Tomohiko Takasaki, Ichiro Kurane, Takashi Kobayashi, Yuki Eshita
Format: Article
Language:English
Published: BMC 2014-03-01
Series:Parasites & Vectors
Subjects:
Online Access:https://doi.org/10.1186/1756-3305-7-143
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author Lucky Ronald Runtuwene
Eiji Konishi
Atsushi Yamanaka
Yoshihiro Makino
Yutaka Suzuki
Tomohiko Takasaki
Ichiro Kurane
Takashi Kobayashi
Yuki Eshita
author_facet Lucky Ronald Runtuwene
Eiji Konishi
Atsushi Yamanaka
Yoshihiro Makino
Yutaka Suzuki
Tomohiko Takasaki
Ichiro Kurane
Takashi Kobayashi
Yuki Eshita
author_sort Lucky Ronald Runtuwene
collection DOAJ
description Abstract Background Dengue virus infection manifests in three distinct forms in humans: dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Infection with the virus is a fatal disease; no vaccine is available and prevention depends on interruption of the chain of transmission. The study of dengue viral transmission by mosquitoes is hindered due to the lack of an affordable animal model. In general, immuno-competent mice are used as a simple and inexpensive animal model, but mice are not susceptible to dengue virus infection and therefore viremia will not occur following the inoculation of the virus in such mice. Here, we report a method for creating artificial viremia in immuno-competent mice, and further demonstrate the use of viremic mice to simultaneously infect a large number of Aedes aegypti. Methods We infected K562 cells with DENV-2 in the presence of an antibody against DENV-4. We then incubated the cells for 2 d before injecting the infected cells into C3H mice. After 5 h incubation, we allowed 100–150 female Aedes aegypti to feed on blood from the mice directly. We collected blood samples from the mice and from randomly selected Ae. aegypti at 2, 6, 12, and 24 h post-blood meal and screened the samples for DENV-2 genome as well as for virus concentration. Results Our procedure provided high virus concentrations in the mice for at least 7 h after viral inoculation. We found that 13 out of 14 randomly picked mosquitoes were infected with DENV-2. High concentrations of virus were detected in the mosquitoes until at least 12 h post-infection. Conclusions Using the viremic immuno-competent mouse, we show that mass infection of Ae. aegypti is achievable. Compared to other infection techniques using direct inoculation, membrane-feeding, or immuno-deficient/humanized mice, we are confident that this method will provide a simpler and more efficient infection technique.
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spelling doaj.art-72467a402bfd4baab67761a96cb26d402023-06-04T11:15:38ZengBMCParasites & Vectors1756-33052014-03-01711610.1186/1756-3305-7-143Dengue transmission model by means of viremic adult immuno-competent mouseLucky Ronald Runtuwene0Eiji Konishi1Atsushi Yamanaka2Yoshihiro Makino3Yutaka Suzuki4Tomohiko Takasaki5Ichiro Kurane6Takashi Kobayashi7Yuki Eshita8Department of Infectious Disease Control, Faculty of Medicine, Oita UniversityBIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol UniversityBIKEN Endowed Department of Dengue Vaccine Development, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Public Health and Epidemiology, Faculty of Medicine, Oita UniversityDepartment of Medical Genome Sciences, The University of TokyoDepartment of Virology I, National Institute of Infectious DiseasesDepartment of Virology I, National Institute of Infectious DiseasesDepartment of Infectious Disease Control, Faculty of Medicine, Oita UniversityDepartment of Infectious Disease Control, Faculty of Medicine, Oita UniversityAbstract Background Dengue virus infection manifests in three distinct forms in humans: dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Infection with the virus is a fatal disease; no vaccine is available and prevention depends on interruption of the chain of transmission. The study of dengue viral transmission by mosquitoes is hindered due to the lack of an affordable animal model. In general, immuno-competent mice are used as a simple and inexpensive animal model, but mice are not susceptible to dengue virus infection and therefore viremia will not occur following the inoculation of the virus in such mice. Here, we report a method for creating artificial viremia in immuno-competent mice, and further demonstrate the use of viremic mice to simultaneously infect a large number of Aedes aegypti. Methods We infected K562 cells with DENV-2 in the presence of an antibody against DENV-4. We then incubated the cells for 2 d before injecting the infected cells into C3H mice. After 5 h incubation, we allowed 100–150 female Aedes aegypti to feed on blood from the mice directly. We collected blood samples from the mice and from randomly selected Ae. aegypti at 2, 6, 12, and 24 h post-blood meal and screened the samples for DENV-2 genome as well as for virus concentration. Results Our procedure provided high virus concentrations in the mice for at least 7 h after viral inoculation. We found that 13 out of 14 randomly picked mosquitoes were infected with DENV-2. High concentrations of virus were detected in the mosquitoes until at least 12 h post-infection. Conclusions Using the viremic immuno-competent mouse, we show that mass infection of Ae. aegypti is achievable. Compared to other infection techniques using direct inoculation, membrane-feeding, or immuno-deficient/humanized mice, we are confident that this method will provide a simpler and more efficient infection technique.https://doi.org/10.1186/1756-3305-7-143Aedes aegyptiDengue virus type 2Mass-infectionViremiaImmuno-competent mouse
spellingShingle Lucky Ronald Runtuwene
Eiji Konishi
Atsushi Yamanaka
Yoshihiro Makino
Yutaka Suzuki
Tomohiko Takasaki
Ichiro Kurane
Takashi Kobayashi
Yuki Eshita
Dengue transmission model by means of viremic adult immuno-competent mouse
Parasites & Vectors
Aedes aegypti
Dengue virus type 2
Mass-infection
Viremia
Immuno-competent mouse
title Dengue transmission model by means of viremic adult immuno-competent mouse
title_full Dengue transmission model by means of viremic adult immuno-competent mouse
title_fullStr Dengue transmission model by means of viremic adult immuno-competent mouse
title_full_unstemmed Dengue transmission model by means of viremic adult immuno-competent mouse
title_short Dengue transmission model by means of viremic adult immuno-competent mouse
title_sort dengue transmission model by means of viremic adult immuno competent mouse
topic Aedes aegypti
Dengue virus type 2
Mass-infection
Viremia
Immuno-competent mouse
url https://doi.org/10.1186/1756-3305-7-143
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