title: Charged amino acids in the AMPV fusion protein have more influence on induced protection than deletion of the SH or G genes.
abstract: Modifications to F, G and SH genes of an avian metapneumovirus (AMPV) field isolate were made by reverse genetics and their virulence and protective capacity were tested in young turkeys. Infection of one-day-old turkeys with a subtype A AMPV neither caused disease nor stimulated detectable protection against subsequent virulent challenge. While serial passage of this virus in tracheal tissue increased virulence, protection stimulated remained moderate. Substitution of the fusion protein from a protective AMPV very minimally increasing virulence but dramatically increased induced protection; and this was associated with five amino acid substitutions all involving charged amino acids which computational analysis predicted to affect protein surface properties but not immunodominant helper T-lymphocyte antigenic sites. When SH or G genes were deleted, viruses caused no disease but still conferred full protection to the majority of turkeys. In the case of the SH deletion, shed virus post-inoculation was undetectable. Partial SH deletions were found to confer protection related to the length of SH open reading frame remaining. Removal of both SH and G genes together produced a virus conferring negligible protection. We conclude that the characteristics of the AMPV fusion protein are important in inducing protection while the SH and G genes under investigation played a lesser role.
authors.affiliation: Department of Comparative Molecular Medicine, School of Veterinary Science, University of Liverpool, Leahurst Campus, Chester High Road, Neston, Cheshire CH64 7TE, UK. cnaylor@liv.ac.uk
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Naylor
authors.forename: Caterina
authors.initials: C
authors.lastname: Lupini
authors.forename: Paul A
authors.initials: PA
authors.lastname: Brown
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002522:Chlorocebus aethiops; D017353:Gene Deletion; D029121:Metapneumovirus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D009924:Organ Culture Techniques; D018184:Paramyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D011201:Poultry Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014422:Turkeys / Q000276:immunology; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014774:Virulence
chemical_list: D011993:Recombinant Fusion Proteins; D014764:Viral Proteins