Naturally Occurring Frameshift Mutations in the tvb Receptor Gene Are Responsible for Decreased Susceptibility of Chicken to Infection with Avian Leukosis Virus Subgroups B, D, and E
Naturally Occurring Frameshift Mutations in the tvb Receptor Gene Are Responsible for Decreased Susceptibility of Chicken to Infection with Avian Leukosis Virus Subgroups B, D, and E
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tvb 受体基因中自然发生的移码突变导致鸡感染禽白血病病毒 B、D 和 E 亚型的易感性降低
DOI：
10.1128/jvi.01770-17
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发表时间：
2017-12
影响因子：
5.4
通讯作者：
Li
中科院分区：
文献类型：
--
作者：
Li Xinjian;Chen Weiguo;Li Hongxing;Dai Zhenkai;Yan Yiming;Zhang Xinheng;Lin Wencheng;Ma Jingyun;Xie Qingmei;Li Xinjian;Chen Weiguo;Li Hongxing;Dai Zhenkai;Yan Yiming;Zhang Xinheng;Lin Wencheng;Ma Jingyun;Xie Qingmei;Zhang Huanmin;Li Aijun;Shu Dingming;Li
摘要鸡禽白血病病毒（ALV）是一组高度相关的病毒，它从一个共同的逆转录病毒祖先进化成六个亚型，A、E和J。这些亚型利用鸡体内四个基因座编码的不同细胞蛋白作为受体进入宿主细胞。暴露于ALV的受试者可能在选择性压力下产生对ALV感染的抗性。事实上，以前已经在鸡的所有四个受体基因座中鉴定出抗性等位基因。tv B基因编码一种受体，该受体决定宿主细胞对ALV亚群B（ALV-B B）、ALV-D和ALV-E的易感性。在这里，我们描述了两个新的等位基因的tvb受体基因，拥有独立的插入外显子4内的每一个鉴定。这些插入导致移码突变，揭示了一个过早的终止密码子，导致突变mRNA的无义介导的衰变和截短Tvb蛋白的产生。结果，我们观察到tvb基因中的移码突变显着降低了截短的Tvb受体对ALV-B、ALV-D和ALV-E包膜糖蛋白的结合亲和力，并显着降低了对ALV-B、ALV-D和ALV-E感染的易感性体外和体内。总之，这些研究结果表明，移码突变可能是一种降低对ALV易感性的分子机制，并增强了我们对病毒-宿主协同进化的理解。禽白血病病毒（ALV）在目前的根除计划实施之前曾给美国家禽业造成毁灭性的经济损失，并且它继续给中国和东南亚的家禽业造成严重的灾难，在那里部署一个完整的根除计划仍然是一个挑战。tv B基因编码亚型B、D和E ALV感染所必需的细胞受体。在本研究中已经鉴定了由移码突变引起的两种tv B等位基因变体，其已经显示在介导亚组B、D和E ALV感染中具有显著降低的功能。与通过疫苗接种控制疱疹病毒引起的疾病不同，鸡中禽白血病的控制完全依赖于病毒根除措施和宿主遗传抗性。这一发现丰富了tvb基因的等位基因库，并扩大了通过选择在不同鸡群中遗传改良ALV抗性的潜力。
ABSTRACT The group of highly related avian leukosis viruses (ALVs) in chickens are thought to have evolved from a common retroviral ancestor into six subgroups, A to E and J. These ALV subgroups use diverse cellular proteins encoded by four genetic loci in chickens as receptors to gain entry into host cells. Hosts exposed to ALVs might be under selective pressure to develop resistance to ALV infection. Indeed, resistance alleles have previously been identified in all four receptor loci in chickens. The tvb gene encodes a receptor, which determines the susceptibility of host cells to ALV subgroup B (ALV-B), ALV-D, and ALV-E. Here we describe the identification of two novel alleles of the tvb receptor gene, which possess independent insertions each within exon 4. The insertions resulted in frameshift mutations that reveal a premature stop codon that causes nonsense-mediated decay of the mutant mRNA and the production of truncated Tvb protein. As a result, we observed that the frameshift mutations in the tvb gene significantly lower the binding affinity of the truncated Tvb receptors for the ALV-B, ALV-D, and ALV-E envelope glycoproteins and significantly reduce susceptibility to infection by ALV-B, ALV-D and ALV-E in vitro and in vivo. Taken together, these findings suggest that frameshift mutation can be a molecular mechanism of reducing susceptibility to ALV and enhance our understanding of virus-host coevolution. IMPORTANCE Avian leukosis virus (ALV) once caused devastating economic loss to the U.S. poultry industry prior the current eradication schemes in place, and it continues to cause severe calamity to the poultry industry in China and Southeast Asia, where deployment of a complete eradication scheme remains a challenge. The tvb gene encodes the cellular receptor necessary for subgroup B, D, and E ALV infection. Two tvb allelic variants that resulted from frameshift mutations have been identified in this study, which have been shown to have significantly reduced functionality in mediating subgroup B, D, and E ALV infection. Unlike the control of herpesvirus-induced diseases by vaccination, the control of avian leukosis in chickens has relied totally on virus eradication measures and host genetic resistance. This finding enriches the allelic pool of the tvb gene and expands the potential for genetic improvement of ALV resistance in varied chicken populations by selection.
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DOI：
--
发表时间：
1997
期刊：
--
影响因子：
--
作者：
L. N. Payne
通讯作者：
L. N. Payne
影响因子：
--
作者：
John M. Coffin
通讯作者：
John M. Coffin
用表达病毒受体结合蛋白的细胞系鉴定新型病毒受体
影响因子：
4.6
作者：
Mei M;Ye J;Qin A;Wang L;Hu X;Qian K;Shao H
通讯作者：
Shao H
影响因子：
5.4
作者：
Plachy, Jiri;Reinisova, Marketa;Hejnar, Jiri
通讯作者：
Hejnar, Jiri
影响因子：
5.4
作者：
Knauss, DJ;Young, JAT
通讯作者：
Young, JAT