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Genetic Diversity and Evolution

Quantifying Antigenic Relationships among the Lyssaviruses

D. L. Horton, L. M. McElhinney, D. A. Marston, J. L. N. Wood, C. A. Russell, N. Lewis, I. V. Kuzmin, R. A. M. Fouchier, A. D. M. E. Osterhaus, A. R. Fooks, D. J. Smith
D. L. Horton
1Rabies and Wildlife Zoonoses, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom
2Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, Cambridge CB2 1DQ, United Kingdom
3Department of Zoology, Cambridge University, Downing Street, Cambridge CB2 3EJ, United Kingdom
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  • For correspondence: d.horton@vla.defra.gsi.gov.uk
L. M. McElhinney
1Rabies and Wildlife Zoonoses, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom
7 The National Centre for Zoonosis Research, University of Liverpool, Leahurst, Chester High Road, Neston CH64 7TE, United Kingdom
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D. A. Marston
1Rabies and Wildlife Zoonoses, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom
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J. L. N. Wood
2Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, Cambridge CB2 1DQ, United Kingdom
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C. A. Russell
3Department of Zoology, Cambridge University, Downing Street, Cambridge CB2 3EJ, United Kingdom
6Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892
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N. Lewis
2Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, Cambridge CB2 1DQ, United Kingdom
3Department of Zoology, Cambridge University, Downing Street, Cambridge CB2 3EJ, United Kingdom
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I. V. Kuzmin
4Centers for Disease Control and Prevention, Division of Viral and Rickettsial Diseases, 1600 Clifton Road, MSG-33, Atlanta, Georgia 30333
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R. A. M. Fouchier
5Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, Netherlands
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A. D. M. E. Osterhaus
5Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, Netherlands
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A. R. Fooks
1Rabies and Wildlife Zoonoses, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom
7 The National Centre for Zoonosis Research, University of Liverpool, Leahurst, Chester High Road, Neston CH64 7TE, United Kingdom
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D. J. Smith
3Department of Zoology, Cambridge University, Downing Street, Cambridge CB2 3EJ, United Kingdom
5Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, Netherlands
6Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892
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DOI: 10.1128/JVI.01153-10
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ABSTRACT

All lyssaviruses cause fatal encephalitis in mammals. There is sufficient antigenic variation within the genus to cause variable vaccine efficacy, but this variation is difficult to characterize quantitatively: sequence analysis cannot yet provide detailed antigenic information, and antigenic neutralization data have been refractory to high-resolution robust interpretation. Here, we address these issues by using state-of-the-art antigenic analyses to generate a high-resolution antigenic map of a global panel of 25 lyssaviruses. We compared the calculated antigenic distances with viral glycoprotein ectodomain sequence data. Although 67% of antigenic variation was predictable from the glycoprotein amino acid sequence, there are in some cases substantial differences between genetic and antigenic distances, thus highlighting the risk of inferring antigenic relationships solely from sequence data at this time. These differences included epidemiologically important antigenic differences between vaccine strains and wild-type rabies viruses. Further, we quantitatively assessed the antigenic relationships measured by using rabbit, mouse, and human sera, validating the use of nonhuman experimental animals as a model for determining antigenic variation in humans. The use of passive immune globulin is a crucial component of rabies postexposure prophylaxis, and here we also show that it is possible to predict the reactivity of immune globulin against divergent lyssaviruses.

  • Copyright © 2010 American Society for Microbiology
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Quantifying Antigenic Relationships among the Lyssaviruses
D. L. Horton, L. M. McElhinney, D. A. Marston, J. L. N. Wood, C. A. Russell, N. Lewis, I. V. Kuzmin, R. A. M. Fouchier, A. D. M. E. Osterhaus, A. R. Fooks, D. J. Smith
Journal of Virology Oct 2010, 84 (22) 11841-11848; DOI: 10.1128/JVI.01153-10

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Quantifying Antigenic Relationships among the Lyssaviruses
D. L. Horton, L. M. McElhinney, D. A. Marston, J. L. N. Wood, C. A. Russell, N. Lewis, I. V. Kuzmin, R. A. M. Fouchier, A. D. M. E. Osterhaus, A. R. Fooks, D. J. Smith
Journal of Virology Oct 2010, 84 (22) 11841-11848; DOI: 10.1128/JVI.01153-10
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KEYWORDS

Antigens, Viral
Lyssavirus
Rhabdoviridae Infections
Viral Proteins

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