State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
China Center for Type Culture Collection, Wuhan University, Wuhan, China.
J Virol. 2018 Apr 13;92(9). doi: 10.1128/JVI.00179-18. Print 2018 May 1.
Viral infection and replication are affected by host cell heterogeneity, but the mechanisms underlying the effects remain unclear. Using single-cell analysis, we investigated the effects of host cell heterogeneity, including cell size, inclusion, and cell cycle, on foot-and-mouth disease virus (FMDV) infection (acute and persistent infections) and replication. We detected various viral genome replication levels in FMDV-infected cells. Large cells and cells with a high number of inclusions generated more viral RNA copies and viral protein and a higher proportion of infectious cells than other cells. Additionally, we found that the viral titer was 10- to 100-fold higher in cells in G/M than those in other cell cycle phases and identified a strong correlation between cell size, inclusion, and cell cycle heterogeneity, which all affected the infection and replication of FMDV. Furthermore, we demonstrated that host cell heterogeneity influenced the adsorption of FMDV due to differences in the levels of FMDV integrin receptors expression. Collectively, these results further our understanding of the evolution of a virus in a single host cell. It is important to understand how host cell heterogeneity affects viral infection and replication. Using single-cell analysis, we found that viral genome replication levels exhibited dramatic variability in foot-and-mouth disease virus (FMDV)-infected cells. We also found a strong correlation between heterogeneity in cell size, inclusion number, and cell cycle status and that all of these characteristics affect the infection and replication of FMDV. Moreover, we found that host cell heterogeneity influenced the viral adsorption as differences in the levels of FMDV integrin receptors' expression. This study provided new ideas for the studies of correlation between FMDV infection mechanisms and host cells.
病毒感染和复制受到宿主细胞异质性的影响，但作用机制仍不清楚。使用单细胞分析，我们研究了宿主细胞异质性（包括细胞大小、包涵体和细胞周期）对口蹄疫病毒（FMDV）感染（急性和持续性感染）和复制的影响。我们检测到 FMDV 感染细胞中存在各种不同的病毒基因组复制水平。大细胞和含有大量包涵体的细胞产生的病毒 RNA 拷贝、病毒蛋白和感染性细胞的比例均高于其他细胞。此外，我们发现处于 G1/M 期的细胞中的病毒滴度比其他细胞周期阶段高 10 到 100 倍，并且发现细胞大小、包涵体和细胞周期异质性之间存在很强的相关性，这些因素都影响了 FMDV 的感染和复制。此外，我们还证明了宿主细胞异质性通过影响 FMDV 整联蛋白受体表达水平的差异来影响 FMDV 的吸附。总之，这些结果进一步加深了我们对口蹄疫病毒在单个宿主细胞中进化的理解。了解宿主细胞异质性如何影响病毒感染和复制非常重要。使用单细胞分析，我们发现口蹄疫病毒（FMDV）感染细胞中的病毒基因组复制水平存在显著的可变性。我们还发现细胞大小、包涵体数量和细胞周期状态的异质性之间存在很强的相关性，所有这些特征都影响了 FMDV 的感染和复制。此外，我们发现宿主细胞异质性通过影响 FMDV 整联蛋白受体表达水平的差异来影响病毒的吸附。这项研究为研究 FMDV 感染机制与宿主细胞之间的相关性提供了新的思路。
