Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.

Chikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for acute to chronic arthralgias and neuropathies. Although it originated in central Africa, recent reports of disease have come from many parts of the world, including the Americas. While limiting human CHIKV cases thro...

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Autores principales:	Brianne M Hibl, Natalie J M Dailey Garnes, Alexander R Kneubehl, Megan B Vogt, Jennifer L Spencer Clinton, Rebecca R Rico-Hesse
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/924cd28ae4dc4e22b1ca58d4d1d30cf2
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spelling	oai:doaj.org-article:924cd28ae4dc4e22b1ca58d4d1d30cf22021-11-25T06:31:47ZMosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.1935-27271935-273510.1371/journal.pntd.0009427https://doaj.org/article/924cd28ae4dc4e22b1ca58d4d1d30cf22021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009427https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Chikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for acute to chronic arthralgias and neuropathies. Although it originated in central Africa, recent reports of disease have come from many parts of the world, including the Americas. While limiting human CHIKV cases through mosquito control has been used, it has not been entirely successful. There are currently no licensed vaccines or treatments specific for CHIKV disease, thus more work is needed to develop effective countermeasures. Current animal research on CHIKV is often not representative of human disease. Most models use CHIKV needle inoculation via unnatural routes to create immediate viremia and localized clinical signs; these methods neglect the natural route of transmission (the mosquito vector bite) and the associated human immune response. Since mosquito saliva has been shown to have a profound effect on viral pathogenesis, we evaluated a novel model of infection that included the natural vector, Aedes species mosquitoes, transmitting CHIKV to mice containing components of the human immune system. Humanized mice infected by 3-6 mosquito bites showed signs of systemic infection, with demonstrable viremia (by qRT-PCR and immunofluorescent antibody assay), mild to moderate clinical signs (by observation, histology, and immunohistochemistry), and immune responses consistent with human infection (by flow cytometry and IgM ELISA). This model should give a better understanding of human CHIKV disease and allow for more realistic evaluations of mechanisms of pathogenesis, prophylaxis, and treatments.Brianne M HiblNatalie J M Dailey GarnesAlexander R KneubehlMegan B VogtJennifer L Spencer ClintonRebecca R Rico-HessePublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009427 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Brianne M Hibl Natalie J M Dailey Garnes Alexander R Kneubehl Megan B Vogt Jennifer L Spencer Clinton Rebecca R Rico-Hesse Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.
description	Chikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for acute to chronic arthralgias and neuropathies. Although it originated in central Africa, recent reports of disease have come from many parts of the world, including the Americas. While limiting human CHIKV cases through mosquito control has been used, it has not been entirely successful. There are currently no licensed vaccines or treatments specific for CHIKV disease, thus more work is needed to develop effective countermeasures. Current animal research on CHIKV is often not representative of human disease. Most models use CHIKV needle inoculation via unnatural routes to create immediate viremia and localized clinical signs; these methods neglect the natural route of transmission (the mosquito vector bite) and the associated human immune response. Since mosquito saliva has been shown to have a profound effect on viral pathogenesis, we evaluated a novel model of infection that included the natural vector, Aedes species mosquitoes, transmitting CHIKV to mice containing components of the human immune system. Humanized mice infected by 3-6 mosquito bites showed signs of systemic infection, with demonstrable viremia (by qRT-PCR and immunofluorescent antibody assay), mild to moderate clinical signs (by observation, histology, and immunohistochemistry), and immune responses consistent with human infection (by flow cytometry and IgM ELISA). This model should give a better understanding of human CHIKV disease and allow for more realistic evaluations of mechanisms of pathogenesis, prophylaxis, and treatments.
format	article
author	Brianne M Hibl Natalie J M Dailey Garnes Alexander R Kneubehl Megan B Vogt Jennifer L Spencer Clinton Rebecca R Rico-Hesse
author_facet	Brianne M Hibl Natalie J M Dailey Garnes Alexander R Kneubehl Megan B Vogt Jennifer L Spencer Clinton Rebecca R Rico-Hesse
author_sort	Brianne M Hibl
title	Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.
title_short	Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.
title_full	Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.
title_fullStr	Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.
title_full_unstemmed	Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.
title_sort	mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/924cd28ae4dc4e22b1ca58d4d1d30cf2
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Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects.

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