Naturally occurring frame-shift mutations in the tvb receptor gene are responsible for decreased susceptibility to subgroups B, D, and E

Authors: LI, XINJIAN - Shandong Agricultural University; CHEN, WEIGUO - Shandong Agricultural University; Zhang, Huanmin; LI, AIJUN - Jinan University; SHU, DINGMING - Guangdong Academy Of Agricultural Sciences; LI, HONGXING - Shandong Agricultural University; DAI, ZHENKAI - Shandong Agricultural University; YAN, YIMING - Shandong Agricultural University; ZHANG, XINHENG - Shandong Agricultural University; LIN, WENCHENG - Shandong Agricultural University; MA, JINGYUN - South China Agricultural University; XIE, QINGMEI - South China Agricultural University

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2017
Publication Date: 12/20/2017
Citation: Li, X., Chen, W., Zhang, H., Li, A., Shu, D., Li, H., Dai, Z., Yan, Y., Zhang, X., Lin, W., Ma, J., Xie, Q. 2017. Naturally occurring frame-shift mutations in the tvb receptor gene are responsible for decreased susceptibility to subgroups B, D, and E. Journal of Virology. 92(8):e01770-17. https://doi.org/10.1128/JVI.01770-17.
DOI: https://doi.org/10.1128/JVI.01770-17

Interpretive Summary: One of the threatful avian tumor viruses to the poultry industry is known as avian leukosis viruses (ALV). There are six subgroups of ALV identified in chickens. Three of the six subgroups of ALV, known as ALV-B, ALV-D, and ALV-E, infect chicken via a chicken cellular receptor protein, which is the product of a single chicken gene, named tvb. This study reports a finding of a new form of the tvb gene that interferes in, instead of mediating, ALV infection, which probably resulted from natural selection pressure over time. This finding provides a new material for genetic improvement on resistance to ALV in chickens by selection, and should widely benefit the poultry industry as well as the consumers.

Technical 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.