Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA.
Biosecurity Research Institute, Kansas State University, Manhattan, Kansas, USA.
Vector Borne Zoonotic Dis. 2022 Nov;22(11):553-558. doi: 10.1089/vbz.2022.0053.
The emergence or re-emergence of several orthobunyaviruses (order: ; family: ), including Cache Valley virus (CVV) and Oropouche virus, warrants the development and evaluation of candidate live-attenuated vaccines (LAVs). Ideally, these vaccines would elicit long-lasting immunity with one single immunization. Since the deletion of two virulence factors, NSs and NSm, has been shown to attenuate the virulence phenotype of orthobunyaviruses, phleboviruses, and nairoviruses, genetic manipulation of the viral genome is considered an effective strategy for the rational design of candidate LAVs for bunyaviruses across multiple families. In addition, the deletion of Rift Valley fever virus NSs and NSm genes has been shown to reduce transmission by mosquitoes. In this study, the ability of a CVV mutant lacking the NSs and NSm genes (2delCVV) to replicate in intrathoracically injected was compared with the parental wild-type CVV (wtCVV) 6V633 strain. In contrast to the robust replication of wtCVV in injected mosquitoes, the multiplication kinetics of the 2delCVV mutant was reduced by more than a 100-fold. These results suggest that the deletion of NSm and NSs genes is a feasible approach to rationally design candidate orthobunyavirus LAVs that are highly attenuated in mosquitoes and, therefore, pose little risk of reversion to virulence and transmission.
几种正粘病毒（目：；科：）的出现或再现，包括卡奇谷病毒（CVV）和奥罗普切病毒，这就需要开发和评估候选减毒活疫苗（LAV）。理想情况下，这些疫苗只需一次免疫就能引发持久的免疫力。由于删除两个毒力因子 NSs 和 NSm 已被证明能减弱正粘病毒、布尼亚病毒和内罗病毒的毒力表型，因此对病毒基因组进行遗传操作被认为是合理设计跨多个家族布尼亚病毒候选 LAV 的有效策略。此外，删除裂谷热病毒 NSs 和 NSm 基因已被证明能降低蚊子的传播能力。在这项研究中，比较了缺乏 NSs 和 NSm 基因的 CVV 突变体（2delCVV）与亲本野生型 CVV（wtCVV）6V633 株在胸腔内注射后的复制能力。与 wtCVV 在注射蚊子中强大的复制能力形成对比的是，2delCVV 突变体的倍增动力学减少了 100 多倍。这些结果表明，删除 NSm 和 NSs 基因是合理设计候选正粘病毒 LAV 的可行方法，这种 LAV 在蚊子中高度减毒，因此几乎没有毒力和传播能力恢复的风险。
