Howe Laryssa, Leroux Caroline, Issel Charles J, Montelaro Ronald C
Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
J Virol. 2002 Nov;76(21):10588-97. doi: 10.1128/jvi.76.21.10588-10597.2002.
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.
马感染马传染性贫血病毒（EIAV）的特征是出现明确的病毒血症波，这与不同病毒群体的顺序演变相关，这些病毒群体显示出广泛的包膜糖蛋白90（gp90）变异；然而，体内包膜进化与体外血清中和表型之间的相关性仍不明确。因此，本研究的目的是利用先前定义的一组来自连续发热期的天然变异EIAV包膜分离株，来表征持续感染期间包膜变异对病毒中和表型的影响，并确定EIAV包膜中和特异性的决定因素。为了评估连续的EIAV包膜变异体的中和表型，我们通过来自感染源小马的纵向免疫血清组，测定了五种变异包膜对中和作用的敏感性。结果表明，在连续发热期观察到的EIAV包膜序列的进化产生了越来越抗中和的表型。为了进一步确定EIAV中和特异性的包膜决定因素，我们检查了一组嵌合包膜构建体的中和特性，这些构建体源自选定的中和敏感和中和抗性包膜变异体之间的相互包膜结构域交换。这些结果表明，EIAV gp90的V3和V4结构域单独赋予血清中和抗性，而除V3和V4之外的其他包膜片段显然是赋予总血清中和敏感性所必需的。这些数据首次清楚地证明了持续感染期间连续的gp90变异在增加包膜中和抗性方面的影响，确定了gp90 V3和V4结构域是抗体中和抗性的主要决定因素，并表明在定义对血清抗体中和的敏感性方面存在明显的复杂协同包膜结构域相互作用。
