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Structural comparison of two strains of foot-and-mouth disease virus subtype O1 and a laboratory antigenic variant, G67

Lea, Susan ; Abu-Ghazaleh, Robin ; Blakemore, Wendy ; Curry, Stephen ; Fry, Elizabeth ; Jackson, Terry ; King, Andrew ; Logan, Derek LU orcid ; Newman, John and Stuart, David (1995) In Structure 3(6). p.571-580
Abstract

Background: Foot-and-mouth disease viruses (FMDVs) are members of the picornavirus family and cause an economically important disease of cloven-hoofed animals. To understand the structural basis of antigenic variation in FMDV, we have determined the structures of two viruses closely related to strain O1BFS whose structure is known.

Results The two new structures are, like O1BFS, both serotype O viruses. The first, O1 Kaüfbeuren (O1K), is a field isolate dating from an outbreak of FMD in Europe in the 1960s. The second, called G67, is a quadruple mutant of O1K, generated in the laboratory, that bears point mutations conferring resistance to neutralization by monoclonal... (More)

Background: Foot-and-mouth disease viruses (FMDVs) are members of the picornavirus family and cause an economically important disease of cloven-hoofed animals. To understand the structural basis of antigenic variation in FMDV, we have determined the structures of two viruses closely related to strain O1BFS whose structure is known.

Results The two new structures are, like O1BFS, both serotype O viruses. The first, O1 Kaüfbeuren (O1K), is a field isolate dating from an outbreak of FMD in Europe in the 1960s. The second, called G67, is a quadruple mutant of O1K, generated in the laboratory, that bears point mutations conferring resistance to neutralization by monoclonal antibodies, specific for each of the four major antigenic sites defined previously. The availability of the three related virus structures permits a detailed analysis of the way amino acid substitutions influence antigenicity. Structural changes are seen to be limited, in general, to the substituted side chain. For example, the GH loop of VP1, a highly antigenic and mobile protuberance which becomes ordered only under reducing conditions, was essentially indistinguishable in the three viruses despite the accumulation of up to four changes within its 15-residue sequence. At one of the other antigenic sites, however, changes between the two field strains did perturb both side-chain and main-chain structures in the vicinity.

Conclusion The conservation of conformation of the GH loop of VP1 adds to the evidence implicating an integrin as the cellular receptor for FMDV, since this loop contains a conserved RGD (Arg-Gly-Asp) sequence structurally similar to the same tripeptide in some other integrin-binding proteins. Structural changes required for the virus to escape neutralization by monoclonal antibodies are generally small. The more extensive type of structural change exhibited by the field isolates probably reflects differing selective pressures operating in vivo and in vitro.

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author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antigenicity,evolutionary strategies, foot-and-mouth disease virus, picornavirus structure
in
Structure
volume
3
issue
6
pages
10 pages
publisher
Cell Press
external identifiers
  • scopus:0029644937
  • pmid:8590018
ISSN
0969-2126
DOI
10.1016/S0969-2126(01)00191-5
language
English
LU publication?
no
id
eb430ed3-0de8-4b59-a01c-9d3617cbe03a
date added to LUP
2022-04-25 11:30:18
date last changed
2024-01-03 10:19:53
@article{eb430ed3-0de8-4b59-a01c-9d3617cbe03a,
  abstract     = {{<p>Background: Foot-and-mouth disease viruses (FMDVs) are members of the picornavirus family and cause an economically important disease of cloven-hoofed animals. To understand the structural basis of antigenic variation in FMDV, we have determined the structures of two viruses closely related to strain O<sub>1</sub>BFS whose structure is known. <br/></p><p>Results The two new structures are, like O<sub>1</sub>BFS, both serotype O viruses. The first, O<sub>1</sub> Kaüfbeuren (O<sub>1</sub>K), is a field isolate dating from an outbreak of FMD in Europe in the 1960s. The second, called G67, is a quadruple mutant of O<sub>1</sub>K, generated in the laboratory, that bears point mutations conferring resistance to neutralization by monoclonal antibodies, specific for each of the four major antigenic sites defined previously. The availability of the three related virus structures permits a detailed analysis of the way amino acid substitutions influence antigenicity. Structural changes are seen to be limited, in general, to the substituted side chain. For example, the GH loop of VP1, a highly antigenic and mobile protuberance which becomes ordered only under reducing conditions, was essentially indistinguishable in the three viruses despite the accumulation of up to four changes within its 15-residue sequence. At one of the other antigenic sites, however, changes between the two field strains did perturb both side-chain and main-chain structures in the vicinity. <br/></p><p>Conclusion The conservation of conformation of the GH loop of VP1 adds to the evidence implicating an integrin as the cellular receptor for FMDV, since this loop contains a conserved RGD (Arg-Gly-Asp) sequence structurally similar to the same tripeptide in some other integrin-binding proteins. Structural changes required for the virus to escape neutralization by monoclonal antibodies are generally small. The more extensive type of structural change exhibited by the field isolates probably reflects differing selective pressures operating in vivo and in vitro.</p>}},
  author       = {{Lea, Susan and Abu-Ghazaleh, Robin and Blakemore, Wendy and Curry, Stephen and Fry, Elizabeth and Jackson, Terry and King, Andrew and Logan, Derek and Newman, John and Stuart, David}},
  issn         = {{0969-2126}},
  keywords     = {{antigenicity,evolutionary strategies; foot-and-mouth disease virus; picornavirus structure}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{571--580}},
  publisher    = {{Cell Press}},
  series       = {{Structure}},
  title        = {{Structural comparison of two strains of foot-and-mouth disease virus subtype O<sub>1</sub> and a laboratory antigenic variant, G67}},
  url          = {{http://dx.doi.org/10.1016/S0969-2126(01)00191-5}},
  doi          = {{10.1016/S0969-2126(01)00191-5}},
  volume       = {{3}},
  year         = {{1995}},
}