APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity
APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity
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APOBEC3A 和 3C 降低人乳头瘤病毒 16 假病毒粒子的感染性
DOI：
10.1016/j.bbrc.2014.12.103
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发表时间：
2015-02-13
影响因子：
3.1
通讯作者：
Muramatsu, Masamichi
中科院分区：
文献类型：
--
作者：
Ahasan, Md Monjurul;Wakae, Kousho;Muramatsu, Masamichi
载脂蛋白B mRNA编辑酶，催化多肽样（APOBEC）蛋白是细胞DNA/RNA编辑酶，其在针对病毒感染的先天性免疫应答中起关键作用。据报道，APOBEC 3（A3）蛋白使人乳头瘤病毒16（HPV 16）的基因组超突变，HPV 16是宫颈癌的病原体。然而，超突变并不影响病毒DNA的维持，使A3对HPV感染的确切作用难以捉摸。在这里，我们检查是否A3蛋白影响病毒粒子装配使用HPV 16假病毒粒子（PsV）生产系统，其中PsV组装从其衣壳蛋白L1/L2的报告质粒在293 FT细胞中。我们发现A3 A或A3 C在293 FT细胞中的共表达大大降低了PsV的感染性。在A3 A而非A3 C存在下组装的PsV的感染性降低归因于双核苷酸报告质粒的拷贝数减少。另一方面，A3 C，而不是A3 A，有效地结合到L1的免疫共沉淀试验，这表明，这种物理相互作用可能会导致降低感染性的PsV组装在A3 C的存在下。这些结果提供了对A3对HPV 16病毒粒子的组装期的抑制作用的机理见解。(C)2015 Elsevier Inc. All rights reserved.
Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) proteins are cellular DNA/RNA-editing enzymes that play pivotal roles in the innate immune response to viral infection. APOBEC3 (A3) proteins were reported to hypermutate the genome of human papillomavirus 16 (HPV16), the causative agent of cervical cancer. However, hypermutation did not affect viral DNA maintenance, leaving the exact role of A3 against HPV infection elusive. Here we examine whether A3 proteins affect the virion assembly using an HPV16 pseudovirion (PsV) production system, in which PsVs are assembled from its capsid proteins L1/L2 encapsidating a reporter plasmid in 293FT cells. We found that co-expression of A3A or A3C in 293FT cells greatly reduced the infectivity of PsV. The reduced infectivity of PsV assembled in the presence of A3A, but not A3C, was attributed to the decreased copy number of the encapsidated reporter plasmid. On the other hand, A3C, but not A3A, efficiently bound to L1 in co-immunoprecipitation assays, which suggests that this physical interaction may lead to reduced infectivity of PsV assembled in the presence of A3C. These results provide mechanistic insights into A3s' inhibitory effects on the assembly phase of the HPV16 virion. (C) 2015 Elsevier Inc. All rights reserved.