Mutations in HPV18 E1^E4 Impact Virus Capsid Assembly, Infectivity Competence, and Maturation.
Mutations in HPV18 E1^E4 Impact Virus Capsid Assembly, Infectivity Competence, and Maturation.
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DOI：
10.3390/v9120385
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发表时间：
2017-12-19
期刊：
影响因子：
--
通讯作者：
Meyers C
中科院分区：
文献类型：
--
作者：
Biryukov J;Myers JC;McLaughlin-Drubin ME;Griffin HM;Milici J;Doorbar J;Meyers C
在人乳头瘤病毒（HPV）生命周期的生产阶段，最高表达的蛋白质是E1 ^E4。它在感染过程中的全部作用仍有待确定。HPV E1 ^E4在病毒生命周期的早期和晚期都有表达，并有助于病毒基因组扩增。为了进一步阐明E1^E4的功能，并确定它是否在病毒衣壳组装和病毒感染性中发挥作用，我们检测了野生型E1^E4以及四种E1^E4截短突变体。我们的研究表明，含有E1^E4最短截短形式（17/18突变体）的HPV 18基因组产生的病毒滴度与野生型病毒相似，并且与含有三种较长E1^E4突变体的病毒粒子相比显著更高。此外，含有最短E1^E4突变的病毒的感染性与野生型相当，并且显著高于其他三种突变体。相反，无论病毒粒子成熟度如何，含有较长E1^E4突变体的病毒的感染性都完全消失。总之，我们的结果首次表明HPV 18 E1 ^E4影响衣壳组装和病毒感染性以及病毒成熟。
The most highly expressed protein during the productive phase of the human papillomavirus (HPV) life cycle is E1^E4. Its full role during infection remains to be established. HPV E1^E4 is expressed during both the early and late stages of the virus life cycle and contributes to viral genome amplification. In an attempt to further outline the functions of E1^E4, and determine whether it plays a role in viral capsid assembly and viral infectivity, we examined wild-type E1^E4 as well as four E1^E4 truncation mutants. Our study revealed that HPV18 genomes containing the shortest truncated form of E1^E4, the 17/18 mutant, produced viral titers that were similar to wild-type virus and significantly higher compared to virions containing the three longer E1^E4 mutants. Additionally, the infectivity of virus containing the shortest E1^E4 mutation was equivalent to wild-type and significantly higher than the other three mutants. In contrast, infectivity was completely abrogated for virus containing the longer E1^E4 mutants, regardless of virion maturity. Taken together, our results indicate for the first time that HPV18 E1^E4 impacts capsid assembly and viral infectivity as well as virus maturation.
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