Immune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease.
Immune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease.
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DOI：
10.1016/j.virol.2007.01.037
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发表时间：
2007-06
期刊：
影响因子：
3.7
通讯作者：
B. Sponseller;Wendy O. Sparks;Y. Wannemuehler;Yuxing Li;Amanda K. Antons;J. Oaks;S. Carpenter
中科院分区：
文献类型：
--
作者：
B. Sponseller;Wendy O. Sparks;Y. Wannemuehler;Yuxing Li;Amanda K. Antons;J. Oaks;S. Carpenter
马传染性贫血病毒（EIAV）的主要中和结构域（PND）位于SU的V3区。PND中的遗传变异被认为在免疫逃逸和EIAV持久性中起重要作用;然而，很少有研究表征疾病不明显阶段SU中的遗传变异。为了更好地了解病毒持久性的机制，我们进行了纵向研究SU变异的小马实验接种强毒EIAVWyo。通过RT-PCR扩增从接种物和从连续血清样品中分离的病毒RNA，克隆，并对单个克隆进行测序。在获得的147个SU克隆中，我们鉴定了71个不同的V3变异体，其分为五个主要的非重叠组，指定为PND-1至PND-5，其与临床疾病的特定阶段分离。将代表每组的基因型插入感染性分子克隆中，并检测嵌合病毒对感染后连续时间的自体血清中和的敏感性。总体而言，在疾病进展期间，存在对中和抗体的耐药性增加的趋势。与感染后期复发相关的PND基因型对类型特异性和广泛中和抗体均具有抗性，并在体外显示出减少的复制表型。这些发现表明，中和抗体在整个感染过程中施加选择性压力，并表明病毒的免疫逃避和持久性策略在面对不断发展和成熟的宿主免疫应答时发生变化。
The principal neutralizing domain (PND) of equine infectious anemia virus (EIAV) is located in the V3 region of SU. Genetic variation in the PND is considered to play an important role in immune escape and EIAV persistence; however, few studies have characterized genetic variation in SU during the inapparent stage of disease. To better understand the mechanisms of virus persistence, we undertook a longitudinal study of SU variation in a pony experimentally inoculated with the virulent EIAVWyo. Viral RNA isolated from the inoculum and from sequential sera samples was amplified by RT-PCR, cloned, and individual clones were sequenced. Of the 147 SU clones obtained, we identified 71 distinct V3 variants that partitioned into five major non-overlapping groups, designated PND-1 to PND-5, which segregated with specific stages of clinical disease. Genotypes representative of each group were inserted into an infectious molecular clone, and chimeric viruses were tested for susceptibility to neutralization by autologous sera from successive times post-infection. Overall, there was a trend for increasing resistance to neutralizing antibody during disease progression. The PND genotype associated with recrudescence late in infection was resistant to both type-specific and broadly neutralizing antibody, and displayed a reduced replication phenotype in vitro. These findings indicate that neutralizing antibody exerts selective pressure throughout infection and suggest that viral strategies of immune evasion and persistence change in the face of an evolving and maturing host immune response.