The genetic variation landscape of African swine fever virus reveals frequent positive selection and adaptive flexibility
The genetic variation landscape of African swine fever virus reveals frequent positive selection and adaptive flexibility
复制标题
DOI：
10.1111/tbed.14018
复制
发表时间：
2021-03-09
影响因子：
4.3
通讯作者：
Qiu, Hua-Ji
中科院分区：
文献类型：
--
作者：
Bao, Yun-Juan;Qiu, Junhui;Qiu, Hua-Ji
非洲猪瘟病毒（ASFV）是一种导致猪群高死亡率和养猪业毁灭性损失的致命疾病。由于对非洲猪瘟的遗传变异以及宿主适应和病毒-宿主相互作用中涉及的遗传因素的了解不足，阻碍了有效疫苗的开发。在这项研究中，我们进行了一项ASFV的元遗传研究，旨在描绘变异景观，并确定具有正选择特征和与宿主适应相关的遗传因素。我们的数据揭示了ASFV的高度遗传变异性，这是由多样化选择和选择性扫描形成的。选择信号在整个基因组中广泛分布，其中29个基因中存在多样化选择，25个基因中存在选择扫描，突出了ASFV适应性进化的强烈信号。对序列特性的进一步研究揭示了选择特征与病毒-宿主相互作用和适应性灵活性之间的联系。具体来说，我们在多样化选择的关键抗原蛋白EP402R的第157位发现了一个位点，该位点位于t细胞应答中与低水平交叉反应相关的细胞毒性t细胞表位上。重要的是，ASFV宿主范围因子MGF360和MGF505两个多基因家族在同源成员中表现出不同的选择，为遗传多样化和适应能力提供了序列池。通过将具有选择特征的基因整合到ASFV与宿主相互作用的统一框架中，我们发现这些基因参与了宿主免疫相互作用和病毒生命周期的多个过程，并可能在规避宿主防御系统和增强适应适应度方面发挥重要作用。我们的发现将有助于加强对非洲猪瘟在宿主中快速传播和适应的遗传基础的理解。
African swine fever virus (ASFV) is a lethal disease agent that causes high mortality in swine population and devastating loss in swine industries. The development of efficacious vaccines has been hindered by the gap in knowledge concerning genetic variation of ASFV and the genetic factors involved in host adaptation and virus-host interactions. In this study, we performed a meta-genetic study of ASFV aiming to profile the variation landscape and identify genetic factors with signatures of positive selection and relevance to host adaptation. Our data reveal a high level of genetic variability of ASFV shaped by both diversifying selection and selective sweep. The selection signatures are widely distributed across the genome with the diversifying selection falling within 29 genes and selection sweep within 25 genes, highlighting strong signals of adaptive evolution of ASFV. Further examination of the sequence properties reveals the link of the selection signatures with virus-host interactions and adaptive flexibility. Specifically, we discovered a site at 157th of the key antigen protein EP402R under diversifying selection, which is located in the cytotoxic T-cell epitope related to the low level of cross-reaction in T-cell response. Importantly, two multigene families MGF360 and MGF505, the host range factors of ASFV, exhibit divergent selection among the paralogous members, conferring sequence pools for genetic diversification and adaptive capability. By integrating the genes with selection signatures into a unified framework of interactions between ASFV and hosts, we showed that the genes are involved in multiple processes of host immune interaction and virus life cycles, and may play crucial roles in circumventing host defence systems and enhancing adaptive fitness. Our findings will allow enhanced understanding of genetic basis of rapid spreading and adaptation of ASFV among the hosts.