Department of Mathematics, Statistics, and Actuarial Science, Butler University, 4600 Sunset Ave, Indianapolis, IN, 46208, USA.
Department of Biological Sciences, Butler University, 4600 Sunset Ave, Indianapolis, IN, 46208, USA.
Bull Math Biol. 2021 Nov 30;84(1):11. doi: 10.1007/s11538-021-00971-8.
Respiratory syncytial virus (RSV) is a leading viral cause of pediatric respiratory infections and early infant mortality. Despite extensive development efforts currently underway, there remain no vaccines available for the prevention of RSV. RSV is an enveloped, negative-strand RNA virus that utilizes two different proteins (G and F) to mediate attachment and entry into host cells. These G and F proteins are the primary determinants of viral strain-specific differences and elicit protective neutralizing antibodies during natural infection in humans. Earlier studies have demonstrated that these proteins play an additional role in regulating the stability of RSV particles in response to temperature and pH. However, it remains unclear how much variability exists in the stability of RSV strains and what contribution changes in temperature and pH make to the clearance of virus during an active infection. In this study, we evaluated the impacts of changes in temperature and pH on the inactivation of four different chimeric recombinant RSV strains that differ exclusively in G and F protein expression. Using these data, we developed predictive mathematical models to examine the specific contributions and variations in susceptibility that exist between viral strains. Our data provide strain-specific clearance rates and temperature-pH landscapes that shed light on the optimal contributions of temperature and pH to viral clearance. These provide new insight into how much variation exists in the clearance of a major respiratory pathogen and may offer new guidance on optimization of viral strains for development of live-attenuated vaccine preparations.
呼吸道合胞病毒（RSV）是导致儿童呼吸道感染和婴儿早期死亡的主要病毒。尽管目前正在进行广泛的开发工作，但仍没有预防 RSV 的疫苗。RSV 是一种包膜的负链 RNA 病毒，利用两种不同的蛋白（G 和 F）介导与宿主细胞的附着和进入。这些 G 和 F 蛋白是病毒株特异性差异的主要决定因素，并在人类自然感染过程中引发保护性中和抗体。早期的研究表明，这些蛋白在调节 RSV 颗粒对温度和 pH 的稳定性方面发挥了额外的作用。然而，目前尚不清楚 RSV 株的稳定性存在多大的可变性，以及温度和 pH 的变化对活跃感染期间病毒清除的贡献有多大。在这项研究中，我们评估了温度和 pH 的变化对四种不同嵌合重组 RSV 株失活的影响，这些株仅在 G 和 F 蛋白表达上存在差异。利用这些数据，我们开发了预测数学模型来研究病毒株之间存在的特定易感性差异和变化。我们的数据提供了株特异性清除率和温度-pH 图谱，阐明了温度和 pH 对病毒清除的最佳贡献。这些为主要呼吸道病原体清除的变异性提供了新的见解，并可能为优化活疫苗株的开发提供新的指导。
