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鉴定和表征具有增强热稳定性的脊髓灰质炎病毒衣壳突变体。

Identification and Characterization of a Poliovirus Capsid Mutant with Enhanced Thermal Stability.

机构信息

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

出版信息

J Virol. 2019 Mar 5;93(6). doi: 10.1128/JVI.01510-18. Print 2019 Mar 15.

DOI:10.1128/JVI.01510-18
PMID:30567995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6401428/
Abstract

Enteric viruses, including poliovirus, are spread by the fecal-oral route. In order to persist and transmit to a new host, enteric virus particles must remain stable once they are in the environment. Environmental stressors such as heat and disinfectants can inactivate virus particles and prevent viral transmission. It has been previously demonstrated that bacteria or bacterial surface glycans can enhance poliovirus virion stability and limit inactivation from heat or bleach. While investigating the mechanisms underlying bacterially enhanced virion thermal stability, we identified and characterized a poliovirus (PV) mutant with increased resistance to heat inactivation. The M132V mutant harbors a single amino acid change in the VP1 capsid coding that is sufficient to confer heat resistance but not bleach resistance. Although the M132V virus was stable in the absence of bacteria or feces at most temperatures, M132V virus was stabilized by feces at very high temperatures. M132V PV had reduced specific infectivity and RNA uncoating compared with those of wild-type (WT) PV, but viral yields in HeLa cells were similar. In orally inoculated mice, M132V had a slight fitness cost since fecal titers were lower and 12.5% of fecal viruses reverted to the WT. Overall, this work sheds light on factors that influence virion stability and fitness. Viruses spread by the fecal-oral route need to maintain viability in the environment to ensure transmission. Previous work indicated that bacteria and bacterial surface polysaccharides can stabilize viral particles and enhance transmission. To explore factors that influence viral particle stability, we isolated a mutant poliovirus that is heat resistant. This mutant virus does not require feces for stability at most temperatures but can be stabilized by feces at very high temperatures. Even though the mutant virus is heat resistant, it is susceptible to inactivation by treatment with bleach. This work provides insight into how viral particles maintain infectivity in the environment.

摘要

肠道病毒,包括脊髓灰质炎病毒,通过粪-口途径传播。为了在环境中持续存在并传播给新宿主,肠道病毒颗粒必须保持稳定。热和消毒剂等环境胁迫因素可以使病毒颗粒失活,防止病毒传播。先前已经证明,细菌或细菌表面糖蛋白可以增强脊髓灰质炎病毒粒子的稳定性并限制其因热或漂白剂而失活。在研究细菌增强病毒粒子热稳定性的机制时,我们鉴定并表征了一种对热失活具有更高抗性的脊髓灰质炎病毒(PV)突变体。M132V 突变体在 VP1 衣壳编码区仅有一个单一的氨基酸变化,足以赋予耐热性,但不赋予耐漂白性。尽管 M132V 病毒在大多数温度下在没有细菌或粪便的情况下是稳定的,但 M132V 病毒在非常高的温度下被粪便稳定。与野生型(WT)PV 相比,M132V PV 的特异性感染力和 RNA 脱壳能力降低,但在 HeLa 细胞中的病毒产量相似。在口服接种的小鼠中,M132V 具有轻微的适应性成本,因为粪便滴度较低,并且 12.5%的粪便病毒回复为 WT。总的来说,这项工作揭示了影响病毒粒子稳定性和适应性的因素。通过粪-口途径传播的病毒需要在环境中保持生存能力以确保传播。先前的工作表明,细菌和细菌表面多糖可以稳定病毒颗粒并增强传播。为了探索影响病毒颗粒稳定性的因素,我们分离出一种耐热的脊髓灰质炎病毒突变体。该突变病毒在大多数温度下不需要粪便即可稳定,但在非常高的温度下可以被粪便稳定。尽管突变病毒耐热,但它易受漂白剂处理的失活。这项工作提供了对病毒颗粒如何在环境中保持感染力的深入了解。

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