Single-Cell Analysis of Foot-and-Mouth Disease Virus

Wang, Hailong; Xin, Xiu; Zheng, Chengchao; Shen, Chao

doi:10.3389/fmicb.2020.00361

Cited by 5 publications

(2 citation statements)

References 92 publications

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“…Our previous experiments demonstrated that the rate and virulence of infection of BHK-21 by the persistent infection virus FMDV-Op is almost indistinguishable from that of FMDV, which excluded viral mutations or defects in the formation of persistent infection cells (Han et al, 2018). And we have known that persistent infection cells are resistant to wild-type FMDV and that viral immune escape factors in host cells might promote the formation of persistent infection cells (Wang et al, 2020). MAPK/p38 and MAPK/ERK-related signaling pathways were active in the late phase of acute infection, and factors associated with viral replication are differentially expressed in persistent infection cells, such that persistent infection cells achieve their resistance to viral replication by downregulating the expression of MAPK14 and Hspb1 in the MAPK signaling pathway (Li et al, 2020).…”

Section: Introductionmentioning

confidence: 95%

Single-Cell Sequencing Yields Insights in the Evolution of Foot-and-Mouth Disease Virus Persistent Infection

Yuan

Wang

et al. 2022

Front. Cell. Infect. Microbiol.

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Foot-and-mouth disease virus (FMDV) could cause acute infection in host cells, or they could coexist with host cells to generate persistent infection. In persistent infection, the virus could survive for a long time in the host and could be transmitted between different host cells. In the case of FMDV-persistent infection cell line, there is a remarkable significant cellular heterogeneity in the FMDV-persistent infection cell line due to differences of viral load in the individual cells within the cell line. However, the mechanisms of FMDV-persistent infection are not well understood. It is now generally accepted that multiple factors contribute to the coevolution of viruses and cells during the course of persistent infection. The outcome would influence the development of persistent FMDV infection conjointly, reaching a state of equilibrium ultimately. Therefore, in order to elucidate the mechanism of cellular heterogeneity in FMDV-persistent infection cell line, single-cell sequencing was performed on BHK-Op, and pseudotime trajectory plot was draw through cell cluster. Based on the cell clusters, we predicted the development and progression of the FMDV-persistent infection. It could be well explained by the fact that, in BHK-Op cells, there are a fraction of infected cells and a fraction of virus-exposed but uninfected bystander cells. By further comparing the transcripts in cell clusters, we found that these genes were involved in changes in ribosome biogenesis, cell cycle, and intracellular signaling including the interferon signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Through comprehensive cross-tabulation analysis of differential expressed genes in various cluster of cells, we identified a high association of Fos, a downstream transcription factor of the MAPK/extracellular signal–regulated kinase (ERK) signaling pathway, with viral replication during the formation of FMDV-persistent infection. Through the further study of Fos, we found that downregulation of Fos facilitates viral clearance during FMDV-persistent infection. Upregulation of c-Raf, which is the upstream of the MAPK/ERK signaling pathway, could promote FMDV replication through downregulation of Fos. Our research is the first to provide insight into the mechanism of the formation FMDV-persistent infection through single-cell sequencing using persistent infection cell line. Pseudotime trajectory analysis was the first time to apply for FMDV-persistent infection cell line. Our work highlights the detailed overview of the evolution of FMDV-persistent infection. We also analyzed the differential expressed genes in the replication or elimination of FMDV within the host. We found that the MAPK/ERK signaling pathway and its downstream transcription factor Fos play an important role in FMDV-persistent infection.

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Section: Introductionmentioning

confidence: 95%

Single-Cell Sequencing Yields Insights in the Evolution of Foot-and-Mouth Disease Virus Persistent Infection

Yuan

Wang

et al. 2022

Front. Cell. Infect. Microbiol.

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“…FMDV genome encodes four structural proteins (VP1, VP2, VP3, and VP4) and at least 10 non-structural proteins (L, 2A, 2B, 2C, 3A, 3B1, 3B2, 3B3, 3C, 3D, and some intermediate precursors) (4). As virion structure components, VP1-VP3 compose the outer capsid, while VP4 is located inside the capsid (5).…”

Section: Introductionmentioning

confidence: 99%

Foot-and-mouth disease virus VP1 promotes viral replication by regulating the expression of chemokines and GBP1

Chen²,

Liu³

et al. 2022

Front. Vet. Sci.

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Foot-and-mouth disease virus (FMDV) is an acute, highly contagious, and economically destructive pathogen of vesicular disease that affects domestic and wild cloven-hoofed animals. The FMDV VP1 protein is an important part of the nucleocapsid and plays a significant role during FMDV infection. However, the signal pathways mediated by VP1 in the life cycle of FMDV and the related mechanisms are not yet fully understood. Here, we performed RNA-seq to compare gene expression profiles between pCAGGS-HA-VP1 transfected PK-15 cells and pCAGGS-HA (empty vector) transfected PK-15 cells. The results showed 5,571 genes with significantly different expression levels, of which 2,981 were up-regulated and 2,590 were down-regulated. GO enrichment analysis showed that 51 GO terms were significantly enriched in cell components including protein complex, membrane and organelle part. KEGG enrichment analysis showed 11 KEGG pathways were significantly enriched which were mainly related to the immune system, infectious viral disease, and signal transduction. Among the up-regulated genes, the chemokines such as CCL5, CXCL8, and CXCL10 in turn promoted FMDV replication. In contrast, GBP1, an interferon-stimulated gene that was suppressed by VP1 and FMDV, could effectively inhibit FMDV replication. Our research provides a comprehensive overview of the response of host cells to VP1 protein and a basis for further research to understand the roles of VP1 in FMDV infection including the genes involved in FMDV replication.

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Binding interactions of acrylamide with lysozyme and its underlying mechanisms based on multi-spectra, isothermal titration microcalorimetry and docking simulation

Chu

Sun

et al. 2021

Journal of Molecular Liquids

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Single-Cell Analysis of Foot-and-Mouth Disease Virus

Cited by 5 publications

References 92 publications

Single-Cell Sequencing Yields Insights in the Evolution of Foot-and-Mouth Disease Virus Persistent Infection

Single-Cell Sequencing Yields Insights in the Evolution of Foot-and-Mouth Disease Virus Persistent Infection

Foot-and-mouth disease virus VP1 promotes viral replication by regulating the expression of chemokines and GBP1

Binding interactions of acrylamide with lysozyme and its underlying mechanisms based on multi-spectra, isothermal titration microcalorimetry and docking simulation

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