Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus.
Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus.
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DOI：
10.3390/v14091964
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发表时间：
2022-09-04
期刊：
影响因子：
--
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Cladel NM;Xu J;Peng X;Jiang P;Christensen ND;Zheng ZM;Hu J
大约5%的人类癌症可归因于人类乳头瘤病毒(HPV)感染。尽管有预防性的HPV疫苗可用，但HPV相关疾病和癌症仍然是世界范围内重大的公共卫生和经济负担。目前对HPV相关疾病和癌症的诊断和治疗主要基于细胞/组织形态检查和/或高危HPV类型的检测。缺乏可靠的靶标/标记物来提高诊断和治疗的准确性。已经建立了几种自然发生的动物乳头瘤病毒模型作为研究HPV发病机制的替代模型。其中，棉尾兔乳头瘤病毒(CRPV)模型已被誉为金标准。这一模式在成功开发现在可用于预防HPV感染的疫苗方面发挥了关键作用。在过去的80年里，CRPV模型被广泛应用于研究HPV的致癌作用。利用一大组具有明显、可重复和可预测表型的CRPV功能突变基因组，我们对肿瘤进展过程中病毒与宿主的相互作用有了更深入的了解。近年来，将全基因组RNA序列分析应用于CRPV模型，使我们能够了解和验证与HPV相关癌症报告的变化平行的变化。此外，我们已经建立了一系列基因修饰的兔系，以促进机制研究和新治疗策略的开发。在本文中，我们总结了一些有意义的发现，这些发现促进了我们对HPV发病机制的理解，并强调了新型基因修饰兔的发展对未来机制研究的意义。
Approximately 5% of all human cancers are attributable to human papillomavirus (HPV) infections. HPV-associated diseases and cancers remain a substantial public health and economic burden worldwide despite the availability of prophylactic HPV vaccines. Current diagnosis and treatments for HPV-associated diseases and cancers are predominantly based on cell/tissue morphological examination and/or testing for the presence of high-risk HPV types. There is a lack of robust targets/markers to improve the accuracy of diagnosis and treatments. Several naturally occurring animal papillomavirus models have been established as surrogates to study HPV pathogenesis. Among them, the Cottontail rabbit papillomavirus (CRPV) model has become known as the gold standard. This model has played a pivotal role in the successful development of vaccines now available to prevent HPV infections. Over the past eighty years, the CRPV model has been widely applied to study HPV carcinogenesis. Taking advantage of a large panel of functional mutant CRPV genomes with distinct, reproducible, and predictable phenotypes, we have gained a deeper understanding of viral–host interaction during tumor progression. In recent years, the application of genome-wide RNA-seq analysis to the CRPV model has allowed us to learn and validate changes that parallel those reported in HPV-associated cancers. In addition, we have established a selection of gene-modified rabbit lines to facilitate mechanistic studies and the development of novel therapeutic strategies. In the current review, we summarize some significant findings that have advanced our understanding of HPV pathogenesis and highlight the implication of the development of novel gene-modified rabbits to future mechanistic studies.
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