Dynamic Co-evolution and Interaction of Avian Leukosis Virus Genetic Variants and Host Immune Responses.
Dynamic Co-evolution and Interaction of Avian Leukosis Virus Genetic Variants and Host Immune Responses.
复制标题
禽白血病病毒遗传变异与宿主免疫反应的动态协同进化和相互作用
DOI：
10.3389/fmicb.2017.01168
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发表时间：
2017
影响因子：
5.2
通讯作者：
Cui Z
中科院分区：
文献类型：
--
作者：
Dong X;Meng F;Hu T;Ju S;Li Y;Sun P;Wang Y;Chen W;Zhang F;Su H;Li S;Cui H;Chen J;Xu S;Fang L;Luan H;Zhang Z;Chang S;Li J;Wang L;Zhao P;Shi W;Cui Z
J亚群禽白血病病毒（ALV-J）是一种典型的逆转录病毒，其特点是存在多种变种和相当大的遗传多样性。以往描述ALV-J变异株进化动力学的研究主要集中在感染早期或少数随机选择的克隆。在这里，我们接种了30个特定的病原体无鸡与相同的创始人ALV-J股票已知的遗传背景。从15只病毒血症鸡中选出6只（3只抗体阳性，3只抗体阴性）鸡。在36周内连续分离病毒，然后使用MiSeq高通量测序平台进行测序。这产生了迄今为止最大的ALV-J数据集，由超过300万个干净的读数组成。结果表明，宿主体液免疫可显著提高ALV-J变异株的遗传多样性。特别是，选择压力促进了ALV-J遗传变异频率的动态比例变化。交叉中和实验表明，沿着显性变异的变化，12周和28周最显性变异对应的感染性克隆的特异性抗体滴度在16周和32周采集的血清中也发生了显著变化。相比之下，在抗体阴性鸡中没有观察到显性变异的转变。此外，我们确定了一个新的gp 85基因的高变区。我们的研究揭示了ALV-J与宿主之间的相互作用，这将有助于疫苗和抗病毒药物的开发。
Subgroup J avian leukosis virus (ALV-J), a typical retrovirus, is characterized of existence of a cloud of diverse variants and considerable genetic diversity. Previous studies describing the evolutionary dynamics of ALV-J genetic variants mainly focused on the early infection period or few randomly selected clones. Here, we inoculated 30 specific-pathogen-free chickens with the same founder ALV-J stock of known genetic background. Six (three antibody positive and three antibody negative) chickens were selected among 15 chickens with viremia. Viruses were serially isolated in 36 weeks and then sequenced using MiSeq high-throughput sequencing platform. This produced the largest ALV-J dataset to date, composed of more than three million clean reads. Our results showed that host humoral immunity could greatly enhance the genetic diversity of ALV-J genetic variants. In particular, selection pressures promoted a dynamic proportional changes in ALV-J genetic variants frequency. Cross-neutralization experiment showed that along with the change of the dominant variant, the antibody titers specific to infectious clones corresponding to the most dominant variants in weeks 12 and 28 have also changed significantly in sera collected in weeks 16 and 32. In contrast, no shift of dominant variant was observed in antibody-negative chickens. Moreover, we identified a novel hypervariable region in the gp85 gene. Our study reveals the interaction between ALV-J and the host, which could facilitate the development of vaccines and antiviral drugs.