Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin

ABSTRACT Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activ...

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Autores principales:	Panisadee Avirutnan, Richard E. Hauhart, Mary A. Marovich, Peter Garred, John P. Atkinson, Michael S. Diamond
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/279688e46b7245ec86fc1f48e0260ec0
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spelling	oai:doaj.org-article:279688e46b7245ec86fc1f48e0260ec02021-11-15T15:38:48ZComplement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin10.1128/mBio.00276-112150-7511https://doaj.org/article/279688e46b7245ec86fc1f48e0260ec02011-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00276-11https://doaj.org/toc/2150-7511ABSTRACT Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. IMPORTANCE Dengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Moreover, we observed a direct correlation with the concentration of MBL in human serum and neutralization of DENV infection. Our studies suggest that common genetic polymorphisms that result in disparate levels and function of MBL in humans may impact DENV infection, pathogenesis, and disease severity.Panisadee AvirutnanRichard E. HauhartMary A. MarovichPeter GarredJohn P. AtkinsonMichael S. DiamondAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 6 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Panisadee Avirutnan Richard E. Hauhart Mary A. Marovich Peter Garred John P. Atkinson Michael S. Diamond Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin
description	ABSTRACT Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. IMPORTANCE Dengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Moreover, we observed a direct correlation with the concentration of MBL in human serum and neutralization of DENV infection. Our studies suggest that common genetic polymorphisms that result in disparate levels and function of MBL in humans may impact DENV infection, pathogenesis, and disease severity.
format	article
author	Panisadee Avirutnan Richard E. Hauhart Mary A. Marovich Peter Garred John P. Atkinson Michael S. Diamond
author_facet	Panisadee Avirutnan Richard E. Hauhart Mary A. Marovich Peter Garred John P. Atkinson Michael S. Diamond
author_sort	Panisadee Avirutnan
title	Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin
title_short	Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin
title_full	Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin
title_fullStr	Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin
title_full_unstemmed	Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin
title_sort	complement-mediated neutralization of dengue virus requires mannose-binding lectin
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/279688e46b7245ec86fc1f48e0260ec0
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Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin

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