title: Naturally occurring mutations at residues 253 and 284 in VP2 contribute to the cell tropism and virulence of very virulent infectious bursal disease virus.
abstract: Infectious bursal disease virus (IBDV) is responsible for the highly contagious infectious bursal disease in chickens. Previously, by blind passage, a vvIBDV Gx strain was attenuated to the Gt strain, and a strain CEF-9 with intermediate characters was obtained during attenuation. Since CEF-9 exhibited only two interesting amino acid mutations (Q253H and A284T) on loops P(DE) and P(FG) at the tip of VP2 spikes, we hypothesized that, either function separately or in combination, they define the cell tropism and virulence of vvIBDV. To test this hypothesis, Q253H and A284T were introduced individually or in combination into VP2 of the Gx or Gt strain to obtain six modified clones. Using reverse genetics, combined mutations of Q253H and A284T could adapt vvIBDV to non-permissive CEF cells (rGx-F9VP2) but any single mutation could not. In vivo, rGx-F9VP2 did not cause mortality while the Gx strain induced 66.7% mortality. Dual evidence from natural and rescued strains identified that the cell tropism of vvIBDV to CEF cells was determined by the combined VP2 mutations Q253H and A284T, but not by single mutation. The two residues were mainly responsible for the virulence of vvIBDV. These findings may be helpful in the design of new tailored IBDV vaccines.
authors.affiliation: Division of Avian Infectious Diseases, National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, 427 Maduan Street, Harbin 150001, PR China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.forename: Honglei
authors.initials: H
authors.lastname: Gao
authors.forename: Yulong
authors.initials: Y
authors.lastname: Gao
authors.forename: Liting
authors.initials: L
authors.lastname: Qin
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018175:Birnaviridae Infections / Q000401:mortality / Q000662:veterinary* / Q000821:virology; D002460:Cell Line; D002645:Chickens; D007243:Infectious bursal disease virus / Q000737:chemistry / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D011201:Poultry Diseases / Q000401:mortality / Q000821:virology*; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D056189:Viral Tropism; D014774:Virulence
chemical_list: D014764:Viral Proteins