The lectin pathway of complement activation contributes to protection from West Nile virus infection

Anja Fuchs; Amelia K. Pinto; Wilhelm J. Schwaeble; Michael S. Diamond

doi:10.1016/j.virol.2011.01.003

The lectin pathway of complement activation contributes to protection from West Nile virus infection

Anja Fuchs, Amelia K. Pinto, Wilhelm J. Schwaeble, Michael S. Diamond

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

The function of the lectin pathway of complement activation in vivo against West Nile virus (WNV) or many other pathogenic viruses has not been defined. Mice deficient in lectin pathway recognition molecules (mannose binding lectin-A (MBL-A) and mannose binding lectin-C (MBL-C)) or the effector enzyme mannan-binding lectin-associated serine protease-2 (MASP-2), were more vulnerable to WNV infection than wild type mice. Compared with studies of mice deficient in factors of the classical or alternative pathway, MBL-A^-/- × MBL-C^-/- or MASP-2^-/- mice showed a less severe course of WNV infection. Indeed, a deficiency in lectin pathway activation did not significantly affect the kinetics of viral spread to the central nervous system (CNS) nor did it profoundly alter generation of adaptive B and T cell immune responses. We conclude that MBL-mediated recognition and lectin pathway activation have important yet subordinate functions in protecting against WNV infection and disease.

Original language	English
Pages (from-to)	101-109
Number of pages	9
Journal	Virology
Volume	412
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2011.01.003
State	Published - Mar 30 2011

Bibliographical note

Funding Information:
We thank E. Mehlhop and M. Vogt for performing pilot studies with the MBL-A −/− × MBL-C −/− mice. We thank C. Tedford (Omeros, Inc) for shipment of the MASP-2 −/− mice. This work was supported by a grant from the NIH (the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research ( U54 AI057160 )).

Funding

We thank E. Mehlhop and M. Vogt for performing pilot studies with the MBL-A −/− × MBL-C −/− mice. We thank C. Tedford (Omeros, Inc) for shipment of the MASP-2 −/− mice. This work was supported by a grant from the NIH (the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research ( U54 AI057160 )).

Funders	Funder number
National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases	U54AI057160
Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research	U54 AI057160

Keywords

Complement
Flavivirus
Immunity
Lectin pathway
Pathogenesis

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2011.01.003

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title = "The lectin pathway of complement activation contributes to protection from West Nile virus infection",

abstract = "The function of the lectin pathway of complement activation in vivo against West Nile virus (WNV) or many other pathogenic viruses has not been defined. Mice deficient in lectin pathway recognition molecules (mannose binding lectin-A (MBL-A) and mannose binding lectin-C (MBL-C)) or the effector enzyme mannan-binding lectin-associated serine protease-2 (MASP-2), were more vulnerable to WNV infection than wild type mice. Compared with studies of mice deficient in factors of the classical or alternative pathway, MBL-A-/- × MBL-C-/- or MASP-2-/- mice showed a less severe course of WNV infection. Indeed, a deficiency in lectin pathway activation did not significantly affect the kinetics of viral spread to the central nervous system (CNS) nor did it profoundly alter generation of adaptive B and T cell immune responses. We conclude that MBL-mediated recognition and lectin pathway activation have important yet subordinate functions in protecting against WNV infection and disease.",

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author = "Anja Fuchs and Pinto, \{Amelia K.\} and Schwaeble, \{Wilhelm J.\} and Diamond, \{Michael S.\}",

note = "Funding Information: We thank E. Mehlhop and M. Vogt for performing pilot studies with the MBL-A −/− × MBL-C −/− mice. We thank C. Tedford (Omeros, Inc) for shipment of the MASP-2 −/− mice. This work was supported by a grant from the NIH (the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research ( U54 AI057160 )).",

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N2 - The function of the lectin pathway of complement activation in vivo against West Nile virus (WNV) or many other pathogenic viruses has not been defined. Mice deficient in lectin pathway recognition molecules (mannose binding lectin-A (MBL-A) and mannose binding lectin-C (MBL-C)) or the effector enzyme mannan-binding lectin-associated serine protease-2 (MASP-2), were more vulnerable to WNV infection than wild type mice. Compared with studies of mice deficient in factors of the classical or alternative pathway, MBL-A-/- × MBL-C-/- or MASP-2-/- mice showed a less severe course of WNV infection. Indeed, a deficiency in lectin pathway activation did not significantly affect the kinetics of viral spread to the central nervous system (CNS) nor did it profoundly alter generation of adaptive B and T cell immune responses. We conclude that MBL-mediated recognition and lectin pathway activation have important yet subordinate functions in protecting against WNV infection and disease.

AB - The function of the lectin pathway of complement activation in vivo against West Nile virus (WNV) or many other pathogenic viruses has not been defined. Mice deficient in lectin pathway recognition molecules (mannose binding lectin-A (MBL-A) and mannose binding lectin-C (MBL-C)) or the effector enzyme mannan-binding lectin-associated serine protease-2 (MASP-2), were more vulnerable to WNV infection than wild type mice. Compared with studies of mice deficient in factors of the classical or alternative pathway, MBL-A-/- × MBL-C-/- or MASP-2-/- mice showed a less severe course of WNV infection. Indeed, a deficiency in lectin pathway activation did not significantly affect the kinetics of viral spread to the central nervous system (CNS) nor did it profoundly alter generation of adaptive B and T cell immune responses. We conclude that MBL-mediated recognition and lectin pathway activation have important yet subordinate functions in protecting against WNV infection and disease.

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The lectin pathway of complement activation contributes to protection from West Nile virus infection

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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