Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo

Abstract In a secondary dengue virus (DENV) infection, the presence of non-neutralizing antibodies (Abs), developed during a previous infection with a different DENV serotype, is thought to worsen clinical outcomes by enhancing viral production. This phenomenon is called antibody-dependent enhanceme...

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Autores principales:	Takeshi Kurosu, Keiko Hanabara, Azusa Asai, Sabar Pambudi, Supranee Phanthanawiboon, Magot Diata Omokoko, Ken-ichiro Ono, Masayuki Saijo, Pongrama Ramasoota, Kazuyoshi Ikuta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d24c59de6d7345e49015206dc1b7a441
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spelling	oai:doaj.org-article:d24c59de6d7345e49015206dc1b7a4412021-12-02T16:18:06ZChimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo10.1038/s41598-020-78639-x2045-2322https://doaj.org/article/d24c59de6d7345e49015206dc1b7a4412020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78639-xhttps://doaj.org/toc/2045-2322Abstract In a secondary dengue virus (DENV) infection, the presence of non-neutralizing antibodies (Abs), developed during a previous infection with a different DENV serotype, is thought to worsen clinical outcomes by enhancing viral production. This phenomenon is called antibody-dependent enhancement (ADE) of infection, and it has delayed the development of therapeutic Abs and vaccines against DENV, as they must be evaluated for the potential to induce ADE. Unfortunately, limited replication of DENV clinical isolates in vitro and in experimental animals hinders this evaluation process. We have, therefore, constructed a recombinant chimeric flavivirus (DV2ChimV), which carries premembrane (prM) and envelope (E) genes of type 2 DENV (DENV-2) R05-624 clinical (Thai) isolate in a backbone of Japanese encephalitis virus (Nakayama strain). DENV E-protein is the most important viral target, not only for neutralizing Abs, but also for infection-enhancing Abs. In contrast to DENV-2 R05-624, DV2ChimV replicated efficiently in cultured mammalian cells and was lethal in interferon-α/β–γ-receptor double-knockout mice. With DV2ChimV, we were able to perform neutralization assays, in vitro and in vivo ADE assays, and in vivo protection assays. These results suggest that the chimeric virus is a powerful tool for evaluation of Abs against DENV.Takeshi KurosuKeiko HanabaraAzusa AsaiSabar PambudiSupranee PhanthanawiboonMagot Diata OmokokoKen-ichiro OnoMasayuki SaijoPongrama RamasootaKazuyoshi IkutaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takeshi Kurosu Keiko Hanabara Azusa Asai Sabar Pambudi Supranee Phanthanawiboon Magot Diata Omokoko Ken-ichiro Ono Masayuki Saijo Pongrama Ramasoota Kazuyoshi Ikuta Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo
description	Abstract In a secondary dengue virus (DENV) infection, the presence of non-neutralizing antibodies (Abs), developed during a previous infection with a different DENV serotype, is thought to worsen clinical outcomes by enhancing viral production. This phenomenon is called antibody-dependent enhancement (ADE) of infection, and it has delayed the development of therapeutic Abs and vaccines against DENV, as they must be evaluated for the potential to induce ADE. Unfortunately, limited replication of DENV clinical isolates in vitro and in experimental animals hinders this evaluation process. We have, therefore, constructed a recombinant chimeric flavivirus (DV2ChimV), which carries premembrane (prM) and envelope (E) genes of type 2 DENV (DENV-2) R05-624 clinical (Thai) isolate in a backbone of Japanese encephalitis virus (Nakayama strain). DENV E-protein is the most important viral target, not only for neutralizing Abs, but also for infection-enhancing Abs. In contrast to DENV-2 R05-624, DV2ChimV replicated efficiently in cultured mammalian cells and was lethal in interferon-α/β–γ-receptor double-knockout mice. With DV2ChimV, we were able to perform neutralization assays, in vitro and in vivo ADE assays, and in vivo protection assays. These results suggest that the chimeric virus is a powerful tool for evaluation of Abs against DENV.
format	article
author	Takeshi Kurosu Keiko Hanabara Azusa Asai Sabar Pambudi Supranee Phanthanawiboon Magot Diata Omokoko Ken-ichiro Ono Masayuki Saijo Pongrama Ramasoota Kazuyoshi Ikuta
author_facet	Takeshi Kurosu Keiko Hanabara Azusa Asai Sabar Pambudi Supranee Phanthanawiboon Magot Diata Omokoko Ken-ichiro Ono Masayuki Saijo Pongrama Ramasoota Kazuyoshi Ikuta
author_sort	Takeshi Kurosu
title	Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo
title_short	Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo
title_full	Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo
title_fullStr	Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo
title_full_unstemmed	Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo
title_sort	chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d24c59de6d7345e49015206dc1b7a441
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Chimeric flavivirus enables evaluation of antibodies against dengue virus envelope protein in vitro and in vivo

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