Interactions of human complement with virus particles containing the Nipah virus glycoproteins

John B Johnson; Hector C Aguilar; Benhur Lee; Griffith D Parks

doi:10.1128/JVI.00193-11

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Interactions of human complement with virus particles containing the Nipah virus glycoproteins

Journal article

Open access

Peer reviewed

Interactions of human complement with virus particles containing the Nipah virus glycoproteins

John B Johnson, Hector C Aguilar, Benhur Lee and Griffith D Parks

Journal of virology, Vol.85(12), pp.5940-5948

06/2011

DOI: https://doi.org/10.1128/JVI.00193-11

Handle:

https://hdl.handle.net/2376/113739

PMCID: PMC3126306

PMID: 21450814

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Abstract

Virion - immunology

Antibody Specificity

Cell Line

Complement Activation

Nipah Virus - pathogenicity

Humans

Glycoproteins - metabolism

Cercopithecus aethiops

Complement System Proteins - immunology

Neutralization Tests

Complement C4 - immunology

Nipah Virus - immunology

Virion - metabolism

Antibodies, Viral - blood

Ephrin-B2 - metabolism

Complement C3 - immunology

Antibodies, Neutralizing - immunology

Animals

Viral Envelope Proteins - metabolism

Antibodies, Viral - immunology

Vero Cells

Antibodies, Neutralizing - blood

Complement is an innate immune response system that most animal viruses encounter during natural infections. We have tested the role of human complement in the neutralization of virus particles harboring the Nipah virus (NiV) glycoproteins. A luciferase-expressing vesicular stomatitis virus (VSV) pseudotype that contained the NiV fusion (F) and attachment (G) glycoproteins (NiVpp) showed dose- and time-dependent activation of human complement through the alternative pathway. In contrast to our findings with other paramyxoviruses, normal human serum (NHS) alone did not neutralize NiVpp infectivity in vitro, and electron microscopy demonstrated no significant deposition of complement component C3 on particles. This lack of NiVpp neutralization by NHS was not due to a global inhibition of complement pathways, since complement was found to significantly enhance neutralization by antibodies specific for the NiV F and G glycoproteins. Complement components C4 and C1q were necessary but not sufficient by themselves for the enhancement of antibody neutralization. Human complement also enhanced NiVpp neutralization by a soluble version of the NiV receptor EphrinB2, and this depended on components in the classical pathway. The ability of complement to enhance neutralization fell into one of two profiles: (i) anti-F monoclonal antibodies showed enhancement only at high and not low antibody concentrations, and (ii) anti-G monoclonal antibodies and EphrinB2 showed enhancement at both high and very low levels of antibody (e.g., 3.1 ng) or EphrinB2 (e.g., 2.5 ng). Together, these data establish the importance of human complement in the neutralization of particles containing the NiV glycoproteins and will help guide the design of more effective therapeutics that harness the potency of complement pathways.

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Title: Interactions of human complement with virus particles containing the Nipah virus glycoproteins
Creators: John B Johnson - Department of Microbiology and Immunology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1064, USA
Hector C Aguilar
Benhur Lee
Griffith D Parks
Publication Details: Journal of virology, Vol.85(12), pp.5940-5948
Academic Unit: Paul G. Allen School for Global Animal Health
Publisher: United States
Grant note: R01 AI069317 / NIAID NIH HHS R21 AI081022 / NIAID NIH HHS U54 AI057157 / NIAID NIH HHS AI081022 / NIAID NIH HHS
Identifiers: 99900547542701842
Language: English
Resource Type: Journal article