Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.

Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infec...

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Autores principales:	Chia Yin Lee, Yiu-Wing Kam, Jan Fric, Benoit Malleret, Esther G L Koh, Celine Prakash, Wen Huang, Wendy W L Lee, Cui Lin, Raymond T P Lin, Laurent Renia, Cheng-I Wang, Lisa F P Ng, Lucile Warter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/337170f92c384631a4a8d845ccd3e033
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spelling	oai:doaj.org-article:337170f92c384631a4a8d845ccd3e0332021-11-18T06:05:04ZChikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.1553-73661553-737410.1371/journal.ppat.1002390https://doaj.org/article/337170f92c384631a4a8d845ccd3e0332011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22144891/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop "groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis.Chia Yin LeeYiu-Wing KamJan FricBenoit MalleretEsther G L KohCeline PrakashWen HuangWendy W L LeeCui LinRaymond T P LinLaurent ReniaCheng-I WangLisa F P NgLucile WarterPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 12, p e1002390 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Chia Yin Lee Yiu-Wing Kam Jan Fric Benoit Malleret Esther G L Koh Celine Prakash Wen Huang Wendy W L Lee Cui Lin Raymond T P Lin Laurent Renia Cheng-I Wang Lisa F P Ng Lucile Warter Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.
description	Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop "groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis.
format	article
author	Chia Yin Lee Yiu-Wing Kam Jan Fric Benoit Malleret Esther G L Koh Celine Prakash Wen Huang Wendy W L Lee Cui Lin Raymond T P Lin Laurent Renia Cheng-I Wang Lisa F P Ng Lucile Warter
author_facet	Chia Yin Lee Yiu-Wing Kam Jan Fric Benoit Malleret Esther G L Koh Celine Prakash Wen Huang Wendy W L Lee Cui Lin Raymond T P Lin Laurent Renia Cheng-I Wang Lisa F P Ng Lucile Warter
author_sort	Chia Yin Lee
title	Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.
title_short	Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.
title_full	Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.
title_fullStr	Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.
title_full_unstemmed	Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.
title_sort	chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/337170f92c384631a4a8d845ccd3e033
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Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.

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