首页> 外文期刊>Journal of Virology >Natural feline leukemia virus variant escapes neutralization by a monoclonal antibody via an amino acid change outside the antibody-binding epitope.
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Natural feline leukemia virus variant escapes neutralization by a monoclonal antibody via an amino acid change outside the antibody-binding epitope.

机译:天然猫型白血病病毒变型通过抗体结合表位外部的氨基酸变化通过单克隆抗体的中和。

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We have molecularly cloned a natural variant of feline leukemia virus subtype B. This isolate is unique in that it is not neutralized by a monoclonal antibody which neutralized all other feline leukemia virus isolates tested, including members of the A, B, and C subtypes. Western immunoblotting indicated that the monoclonal antibody was less able to bind to the gp70 of the resistant isolate (designated lambda B1) than to the gp70s of susceptible viruses. Nucleotide sequence analysis of the envelope gene of lambda B1 revealed a high degree of homology with the susceptible Snyder-Theilen, Gardner-Arnstein, and Rickard subtype B isolates, including the presence of a 5-amino-acid minimal binding epitope required for binding by the neutralizing monoclonal antibody. The only change within the vicinity of this epitope was in a single nucleotide, and this difference changed a proline residue to leucine three amino acids from the N terminus of the binding epitope. Competitive binding studies with synthetic peptides indicated that substitution of leucine for proline resulted in a 10-fold decrease in the ability of the peptide to compete for antibody binding to native antigen. The results are consistent with the interpretation that this amino acid change lowers the affinity of antibody binding, resulting in failure of the antibody to neutralize the variant virus.
机译:我们分子克隆了一种猫型白血病病毒亚型B的天然变体。该分离物是独特的,因为它不受单克隆抗体中和的是所测试的所有其他猫的白血病病毒分离物,包括A,B和C亚型的成员。 Western免疫印迹表明单克隆抗体较不能够与抗性分离物(指定的Lambda B1)的GP70结合到易感病毒的GP70。 Lambda B1的封装基因的核苷酸序列分析揭示了易感Snyder-Thiilen,Gardner-Arnstein和Rickard亚型B分离物的高度同源性,包括所需的5-氨基酸最小结合表位的存在中和单克隆抗体。该表位附近的唯一变化在单个核苷酸中,并且这种差异将脯氨酸残基改变为从结合表位的N末端亮氨酸三个氨基酸。具有合成肽的竞争性结合研究表明,肽的亮氨酸取代导致肽的能力降低,肽竞争与天然抗原的抗体结合。结果与解释一致,即该氨基酸变化降低了抗体结合的亲和力,导致抗体失效中和变体病毒。

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