Key result
Host cell heterogeneity, specifically larger cell size, higher inclusion number, and G2/M cell cycle phase, significantly increased Foot-and-Mouth Disease Virus replication and infectious viral titer.
Host cell heterogeneity, including cell size, inclusion number, and cell cycle status, significantly affects foot-and-mouth disease virus infection, replication, and adsorption.
Cell cycle status may modulate FMDV yields; extends host heterogeneity insights but leaves open in vivo validation.
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 2 /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. IMPORTANCE 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.
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Xin et al. (2018) studied Foot-and-Mouth Disease Virus (FMDV) infection. Host cell heterogeneity (cell size, inclusion number, cell cycle) vs. Smaller cells, fewer inclusions, or other cell cycle phases was evaluated on Viral RNA copies and infectious viral titer. Host cell heterogeneity, specifically larger cell size, higher inclusion number, and G2/M cell cycle phase, significantly increased Foot-and-Mouth Disease Virus replication and infectious viral titer.
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