2018年 2月14日，國際學(xué)術(shù)期刊《Journal of Virology》（IF=4.66）在線(xiàn)發(fā)表了病毒學(xué)國家重點(diǎn)實(shí)驗室鄭從義教授團隊的最新研究成果，論文題為Single-cell analysis of the impact of host-cell heterogeneity on infection with foot and mouth disease virus.（《單細胞分析宿主細胞異質(zhì)性對口蹄疫病毒感染的影響》）。該工作揭示了宿主細胞的異質(zhì)性如何對口蹄疫病毒感染產(chǎn)生影響。
細胞異質(zhì)性在很多生命活動(dòng)中普遍存在，在同一瓶培養的細胞中也會(huì )存在顯著(zhù)的異質(zhì)性。鄭從義教授實(shí)驗室的前期研究發(fā)現，在單個(gè)細胞中不論病毒還是宿主基因的表達均存在較大的差異。為了找到這些差異的原因，在本研究中，采用流式細胞分選技術(shù)，從細胞的大小、內含物的多少以及細胞周期三個(gè)方面進(jìn)行分析，發(fā)現在大的細胞、高內含物的細胞以及G2/M期細胞中，能夠感染更多的病毒。通過(guò)單細胞的分析，研究發(fā)現病毒感染的差異，在病毒吸附階段就顯現出來(lái)，進(jìn)一步的分析表明，是由于不同異質(zhì)性細胞表面的病毒受體表達差異造成的，而病毒受體表達差異可能是由細胞周期引起的。本研究為進(jìn)一步分析宿主細胞在病毒感染中的作用提供了新的思路。
圖示：?jiǎn)渭毎治鼋沂炯毎愘|(zhì)性影響FMDV感染
博士生辛秀為該論文的第一作者，沈超老師為通訊作者。該工作得到了國家重點(diǎn)基礎研究發(fā)展計劃、國家自然科學(xué)基金和國家科技基礎條件平臺建設項目的支持。
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 variable viral genome replication levels in FMDV-infected cells. Larger cells and cells with a greater number of inclusions generated more viral RNA copies, viral protein, and a higher proportion of infectious cells. Additionally, we found that the viral titer was 10- to 100-fold higher in cells in G2/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 mouth disease virus (FMDV)-infected cells. We also found that 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.
本期編輯：Tony
來(lái)源：病毒學(xué)國家重點(diǎn)實(shí)驗室
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