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Journal of Virology, November 2002, p. 10588-10597, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10588-10597.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

Laryssa Howe,1 Caroline Leroux,2 Charles J. Issel,3 and Ronald C. Montelaro1,2,{dagger}*

Department of Infectious Disease and Microbiology, Graduate School of Public Health,1 Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261,2 Department of Veterinary Sciences, Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 405463

Received 10 April 2002/ Accepted 25 July 2002

Equine infectious anemia virus (EIAV) infection of horses is characterized by well-defined waves of viremia associated with the sequential evolution of distinct viral populations displaying extensive envelope gp90 variation; however, a correlation of in vivo envelope evolution with in vitro serum neutralization phenotype remains undefined. Therefore, the goal of the present study was to utilize a previously defined panel of natural variant EIAV envelope isolates from sequential febrile episodes to characterize the effects of envelope variation during persistent infection on viral neutralization phenotypes and to define the determinants of EIAV envelope neutralization specificity. To assess the neutralization phenotypes of the sequential EIAV envelope variants, we determined the sensitivity of five variant envelopes to neutralization by a longitudinal panel of immune serum from the source infected pony. The results indicated that the evolution of the EIAV envelope sequences observed during sequential febrile episodes produced an increasingly neutralization-resistant phenotype. To further define the envelope determinants of EIAV neutralization specificity, we examined the neutralization properties of a panel of chimeric envelope constructs derived from reciprocal envelope domain exchanges between selected neutralization-sensitive and neutralization-resistant envelope variants. These results indicated that the EIAV gp90 V3 and V4 domains individually conferred serum neutralization resistance while other envelope segments in addition to V3 and V4 were evidently required for conferring total serum neutralization sensitivity. These data clearly demonstrate for the first time the influence of sequential gp90 variation during persistent infection in increasing envelope neutralization resistance, identify the gp90 V3 and V4 domains as the principal determinants of antibody neutralization resistance, and indicate distinct complex cooperative envelope domain interactions in defining sensitivity to serum antibody neutralization.

* Corresponding author. Mailing address: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1144 Biomedical Science Tower, Pittsburgh, PA 15261. Phone: (412) 648-8869. Fax: (412) 383-8859. E-mail: rmont{at}pitt.edu.

{dagger} Present address: UMR 754 INRA-UCBL-ENVL, Rétrovirus et Pathologie Comparée, Lyon, France.

Journal of Virology, November 2002, p. 10588-10597, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10588-10597.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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