Hu Jiafen, Cladel Nancy M, Christensen Neil D
Department of Pathology, Jake Gittlen Cancer Research Foundation, Hershey, Pennsylvania, USA.
Viral Immunol. 2007 Summer;20(2):320-5. doi: 10.1089/vim.2006.0104.
Our previous studies showed that a progressive cottontail rabbit papillomavirus (CRPV) strain containing a single amino acid change in E6 (E6G252E) induced papilloma regression in EIII/JC inbred rabbits. This finding implied that the point mutation might cause an increase in the antigenicity of the mutant versus the wild-type E6. To test this hypothesis, groups of four EIII/JC inbred rabbits were immunized with wild-type CRPVE6, CRPVE6G252E, CRPV E5, or with vector alone. A gene gun delivery system was used to deliver the DNA vaccines. Two of four rabbits from both E6G252E- and wild-type E6-vaccinated groups were free of papillomas at week 12 after viral challenge. Significantly smaller papillomas were found on E6G252E-vaccinated rabbits than on E6-, E5-, and control vector-vaccinated rabbits (p = 0.01, unpaired Student t test) and these small papillomas regressed at week 20 after viral challenge. E5 vaccination failed to provide protection against viral challenge, and the mean papilloma size was also comparable to that of the control vector-vaccinated rabbits (p > 0.05, unpaired Student t test). We conclude that a single amino acid change in the CRPV E6 protein (G252E) increased protection against wild-type infectious CRPV.
我们之前的研究表明，一种在E6蛋白中有单个氨基酸变化（E6G252E）的进行性棉尾兔乳头瘤病毒（CRPV）毒株，能诱导EIII/JC近交系兔的乳头瘤消退。这一发现暗示该点突变可能导致突变型E6相对于野生型E6的抗原性增加。为了验证这一假设，将四组EIII/JC近交系兔分别用野生型CRPV E6、CRPV E6G252E、CRPV E5或仅用载体进行免疫。使用基因枪递送系统来递送DNA疫苗。在病毒攻击后第12周，E6G252E免疫组和野生型E6免疫组的四只兔子中有两只没有出现乳头瘤。在E6G252E免疫的兔子身上发现的乳头瘤明显小于E6、E5和对照载体免疫的兔子（p = 0.01，非配对学生t检验），并且这些小乳头瘤在病毒攻击后第20周消退。E5免疫未能提供针对病毒攻击的保护，其乳头瘤平均大小也与对照载体免疫的兔子相当（p > 0.05，非配对学生t检验）。我们得出结论，CRPV E6蛋白中的单个氨基酸变化（G252E）增强了对野生型感染性CRPV的保护作用。
