Impact of genetic changes to the CRPV genome and their application to the study of pathogenesis in vivo
Impact of genetic changes to the CRPV genome and their application to the study of pathogenesis in vivo
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DOI：
10.1016/j.virol.2006.08.045
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发表时间：
2007-02-20
期刊：
影响因子：
3.7
通讯作者：
Christensen, Neil D.
中科院分区：
文献类型：
--
作者：
Hu, Jiafen;Cladel, Nancy M.;Christensen, Neil D.
棉尾兔乳头瘤病毒(CRPV)/兔模型已被用于研究乳头瘤病毒基因组中不同抗原的致瘤性和免疫原性，从而为开发预防和治疗乳头瘤病毒感染的疫苗提供了一个临床前模型。CRPV模型的一个独特特性是，感染可以通过病毒DNA启动。这一特性允许在体内对病毒突变体进行功能测试。我们在CRPV基因组的所有不同编码区和非编码区引入了点突变、插入和缺失，并在这个模型中测试了它们的传染性。我们发现，大多数突变基因组都保持了活力，并能诱发家兔乳头状瘤。这些数据表明，CRPV基因组可以耐受许多修改，而不会影响其引发皮肤乳头状瘤的能力。结合我们最近建立的人类白细胞抗原-A2.1转基因兔模型，这种可塑性使我们能够将CRPV/兔模型扩展到从其他人类病毒和肿瘤抗原中筛选出人类白细胞抗原-A2.1限制性表位。(C)2006 Elsevier Inc.保留所有权利。
The cottontail rabbit papillomavims (CRPV)/rabbit model has been used to study oncogenicity and immunogenicity of different antigens from the papillomavirus genome and has therefore served as a preclinical model for the development of preventive and therapeutic vaccines against papillomavirus infections. One unique property of the CRPV model is that infection can be initiated using viral DNA. This property allows for the functional testing of viral mutants in vivo. We have introduced point mutations, insertions and deletions into all of the different coding and noncoding regions of the CRPV genome and have tested their infectivity in this model. We found that the majority of the mutant genomes retained viability and could induce papillomas in domestic rabbits. These data indicated that the CRPV genome is tolerant of many modifications without compromising its ability to initiate skin papillomas. In combination with our recently established HLA-A2.1 transgenic rabbit model, this plasticity allows us to extend the utility of the CRPV/rabbit model to the screening of HLA-A2.1 restricted epitopes from other human viral and tumor antigens. (c) 2006 Elsevier Inc. All rights reserved.