title: Attenuation of chicken anemia virus by site-directed mutagenesis of VP2.
abstract: Chicken anemia virus (CAV) is a significant immunosuppressive pathogen of chickens, but relatively little is known about the effect of specific mutations on its virulence. In order to study the virulence of CAV, an infection model was developed in embryos. Significant growth depression, measured as a reduction in mean body weight, was found for wild-type CAV infection. Infection with wild-type CAV resulted in a significant reduction in thymic and splenic weights and consistently produced severe lesions in the thymus, spleen and bone marrow, as well as haemorrhages. CAVs mutated in the VP2 gene were infectious for embryos, but were highly attenuated with respect to growth depression and CAV-specific pathology. Relative to wild-type infection, viruses Mut C86R, Mut R101G, Mut H103Y, Mut R129G, Mut Q131P, Mut R/K/K150/151/152G/A/A, Mut D/E161/162G/G and Mut E186G were highly attenuated, and viruses Mut L163P and Mut D169G were moderately attenuated. Attenuation of the ability to produce lesions was found consistently for the thymus, spleen and bone marrow, thymic and splenic weights, and for CAV-induced haemorrhage. There was no growth depression associated with infection by the group of highly attenuated mutant viruses and a moderate reduction in mean body weight was only found for virus Mut L163P. These findings show that mutations in the VP2 gene can reduce the virulence of CAV and these mutant viruses may have value as vaccine candidates.
authors.affiliation: Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Peters
authors.affiliation: Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria 3050, Australia.
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.affiliation: Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Tivendale
authors.affiliation: Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Browning
mesh_terms: D000818:Animals; D002060:Bursa of Fabricius / Q000473:pathology; D036022:Capsid Proteins / Q000235:genetics*; D002642:Chick Embryo; D017727:Chicken anemia virus / Q000235:genetics / Q000472:pathogenicity; D002645:Chickens; D018173:Circoviridae Infections / Q000473:pathology / Q000662:veterinary*; D016297:Mutagenesis, Site-Directed; D009929:Organ Size; D011201:Poultry Diseases / Q000473:pathology*; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D014774:Virulence
chemical_list: D036022:Capsid Proteins; C442521:VP2 protein, Chicken anemia virus