title: Incorporation of host complement regulatory proteins into Newcastle disease virus enhances complement evasion.
abstract: Newcastle disease virus (NDV), an avian paramyxovirus, is inherently tumor selective and is currently being considered as a clinical oncolytic virus and vaccine vector. In this study, we analyzed the effect of complement on the neutralization of NDV purified from embryonated chicken eggs, a common source for virus production. Fresh normal human serum (NHS) neutralized NDV by multiple pathways of complement activation, independent of neutralizing antibodies. Neutralization was associated with C3 deposition and the activation of C2, C3, C4, and C5 components. Interestingly, NDV grown in mammalian cell lines was resistant to complement neutralization by NHS. To confirm whether the incorporation of regulators of complement activity (RCA) into the viral envelope afforded complement resistance, we grew NDV in CHO cells stably transfected with CD46 or HeLa cells, which strongly express CD46 and CD55. NDV grown in RCA-expressing cells was resistant to complement by incorporating CD46 and CD55 on virions. Mammalian CD46 and CD55 molecules on virions exhibited homologous restriction, since chicken sera devoid of neutralizing antibodies to NDV were able to effectively neutralize these virions. The incorporation of chicken RCA into NDV produced in embryonated eggs similarly provided species specificity toward chicken sera.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
authors.forename: Moanaro
authors.initials: M
authors.lastname: Biswas
authors.forename: John B
authors.initials: JB
authors.lastname: Johnson
authors.forename: Sandeep R P
authors.initials: SR
authors.lastname: Kumar
authors.forename: Griffith D
authors.initials: GD
authors.lastname: Parks
authors.forename: Subbiah
authors.initials: S
authors.lastname: Elankumarana
authors.forename: Elankumaran
authors.initials: E
authors.lastname: Subbiah
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000235:genetics*; D016466:CHO Cells; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D051916:Membrane Cofactor Protein / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D009500:Neutralization Tests; D009522:Newcastle disease virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013045:Species Specificity; D014461:Ultracentrifugation; D014709:Vero Cells; D014771:Virion / Q000235:genetics* / Q000648:ultrastructure
chemical_list: D018958:CD55 Antigens; D051916:Membrane Cofactor Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D003165:Complement System Proteins