Foot-and-mouth disease (FMD) is an economically devastating animal disease. Adapting the field virus to cells is critical to the vaccine production of FMD viruses (FMDV), and heparan sulfate (HS) and Jumonji C-domain-containing protein 6 (JMJD6) are alternative receptors of cell-adapted FMDV. We performed serial passages of FMDV O/SKR/Andong/2010, classified as the O/Mya-98 topotype/lineage and known as a highly virulent strain, to develop a vaccine seed virus. We traced changes in the amino acid sequences of the P1 region, plaque phenotypes, and the receptor usage of the viruses, and then structurally analyzed the mutations. VP3 H56R and D60G mutations were observed in viruses using the HS receptor and led to changes in the hydrogen bonding between VP3 56 and 60. A VP1 P208L mutation was observed in the virus using the JMJD6 receptor during cell adaptation, enabling the interaction with JMJD6 through the formation of a new hydrogen bond with JMJD6 residue 300. Furthermore, VP1 208 was near the VP1 95/96 amino acids, previously reported as critical mutations for JMJD6 receptor interactions. Thus, the mutation at VP1 208 could be critical for cell adaptation related to the JMJD6 receptor and may serve as a basis for mechanism studies on FMDV cell adaptation.

中文翻译：

---

使用硫酸乙酰肝素和JMJD6受体分析口蹄疫病毒O型血清型的氨基酸突变。

口蹄疫（FMD）是一种经济上具有破坏性的动物疾病。使田间病毒适应细胞对于FMD病毒（FMDV）疫苗的生产至关重要，而硫酸乙酰肝素（HS）和Jumonji C域蛋白6（JMJD6）是适应细胞的FMDV的替代受体。我们进行了FMDV O / SKR / Andong / 2010的连续传代，以鉴定疫苗种子病毒，该传代被归类为O / Mya-98拓扑型/谱系，被称为高毒力毒株。我们追踪了P1区氨基酸序列，噬菌斑表型和病毒受体使用情况的变化，然后从结构上分析了突变。使用HS受体在病毒中观察到VP3 H56R和D60G突变，并导致VP3 56和60之间的氢键发生变化。在细胞适应过程中使用JMJD6受体在病毒中观察到VP1 P208L突变，从而通过与JMJD6残基300形成新的氢键而与JMJD6相互作用。此外，VP1 208接近VP1 95/96氨基酸，以前报告为JMJD6受体相互作用的关键突变。因此，VP1 208的突变对于与JMJD6受体相关的细胞适应可能至关重要，并且可以作为FMDV细胞适应机制研究的基础。