Increasing Type 1 Poliovirus Capsid Stability by Thermal Selection.
Increasing Type 1 Poliovirus Capsid Stability by Thermal Selection.
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DOI：
10.1128/jvi.01586-16
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发表时间：
2017-02-15
影响因子：
5.4
通讯作者：
Rowlands DJ
中科院分区：
文献类型：
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作者：
Adeyemi OO;Nicol C;Stonehouse NJ;Rowlands DJ
脊髓灰质炎是由脊髓灰质炎病毒（PV）引起的高度传染性疾病。它可能导致瘫痪并可能致命。使用减毒口服 (OPV) 和/或灭活 (IPV) PV 疫苗的全球综合免疫计划系统地减少了其传播，并为根除铺平了道路。根除后将继续进行免疫接种，以确保不会再次出现疾病，但 OPV 和 IPV 都存在生物安全问题。这些问题可以通过生产和使用无病毒的病毒样颗粒（VLP）疫苗来解决，该疫苗模仿病毒感染中通常产生的“空”衣壳（EC）。尽管 EC 在抗原上与成熟病毒颗粒无法区分，但它们稳定性较差，很容易转化为不适合疫苗目的的替代构象。稳定的 EC，重组表达为 VLP，可能是无脊髓灰质炎世界的理想候选疫苗。然而，尽管无基因组PV EC已在多种系统中表达为VLP，但其固有的抗原不稳定性已被证明是进一步开发的障碍。在本研究中，我们选择了 1 型 PV (PV-1) 的热稳定 EC。 EC 在高于野生型 (wt) 病毒体转化温度的温度下具有抗原稳定性。我们已经确定了衣壳表面和内部网络中与 EC 稳定性有关的突变。参考衣壳结构，我们推测这些残基在衣壳稳定性中的作用，并假设这种稳定的VLP可以用作新型疫苗。重要性 脊髓灰质炎是一种由真性红斑狼疮引起的高度传染性疾病，即将被消灭。目前的疫苗需要活病毒来生产，因此存在生物安全问题。重组表达的病毒样颗粒（VLP）可以解决这些固有问题。然而，wt PV 的无基因组衣壳 (EC) 不稳定，很容易将抗原性改变为不适合作为疫苗的形式。在这里，我们证明可以通过选择耐热病毒来稳定 1 型 PV 的 EC。我们的数据表明，一些衣壳突变可以稳定 EC，并且可以作为合成稳定 VLP 的候选者，作为未来的无基因组脊髓灰质炎病毒疫苗。
Poliomyelitis is a highly infectious disease caused by poliovirus (PV). It can result in paralysis and may be fatal. Integrated global immunization programs using live-attenuated oral (OPV) and/or inactivated (IPV) PV vaccines have systematically reduced its spread and paved the way for eradication. Immunization will continue posteradication to ensure against reintroduction of the disease, but there are biosafety concerns for both OPV and IPV. They could be addressed by the production and use of virus-free virus-like particle (VLP) vaccines that mimic the “empty” capsids (ECs) normally produced in viral infection. Although ECs are antigenically indistinguishable from mature virus particles, they are less stable and readily convert into an alternative conformation unsuitable for vaccine purposes. Stabilized ECs, expressed recombinantly as VLPs, could be ideal candidate vaccines for a polio-free world. However, although genome-free PV ECs have been expressed as VLPs in a variety of systems, their inherent antigenic instability has proved a barrier to further development. In this study, we selected thermally stable ECs of type 1 PV (PV-1). The ECs are antigenically stable at temperatures above the conversion temperature of wild-type (wt) virions. We have identified mutations on the capsid surface and in internal networks that are responsible for EC stability. With reference to the capsid structure, we speculate on the roles of these residues in capsid stability and postulate that such stabilized VLPs could be used as novel vaccines. IMPORTANCE Poliomyelitis is a highly infectious disease caused by PV and is on the verge of eradication. There are biosafety concerns about reintroduction of the disease from current vaccines that require live virus for production. Recombinantly expressed virus-like particles (VLPs) could address these inherent problems. However, the genome-free capsids (ECs) of wt PV are unstable and readily change antigenicity to a form not suitable as a vaccine. Here, we demonstrate that the ECs of type 1 PV can be stabilized by selecting heat-resistant viruses. Our data show that some capsid mutations stabilize the ECs and could be applied as candidates to synthesize stable VLPs as future genome-free poliovirus vaccines.