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Single-cell RNA-sequencing analysis identifies host long noncoding RNA MAMDC2-AS1 as a co-factor for HSV-1 nuclear transport
- Source :
- International Journal of Biological Sciences
- Publication Year :
- 2020
- Publisher :
- Ivyspring International Publisher, 2020.
-
Abstract
- Herpes simplex virus (HSV) type 1 (HSV-1) infection exhibited high heterogeneity at individual cells level, including the different gene expression patterns and varying amounts of progeny virus. However, the underlying mechanism of such variability remains obscure. The importance of host long noncoding RNAs (lncRNAs) in virus infection had been recognized, while the contribution of lncRNAs to the heterogeneous infection remains unknown. Herein, a prior single-cell RNA sequencing data using HSV-1 reporter strain expressing ICP4-YFP was re-analyzed to obtain the differentially expressed lncRNA between the successfully initiated viral gene expression (ICP4-YFP+) cells and the aborted infection cells (ICP4-YFP-). The ICP4-YFP+ population show a higher abundance of MAMDC2 antisense 1 (MAMDC2-AS1) lncRNA than ICP4-YFP- population. MAMDC2-AS1 silencing reduces the expression of HSV-1 immediate early (IE) genes and limit HSV-1 infection in human host cells. Consistently, ectopic expression of MAMDC2-AS1 enhances HSV-1 IE genes transcription and facilitates the formation of HSV-1-induced plaques. Mechanically, both RNA-pull down and RNA immunoprecipitation assays show that MAMDC2-AS1 interacts with the RNA binding protein heat shock protein 90α (Hsp90α), a molecular chaperone involving in the nuclear import of HSV-1. The MAMDC2-AS1-Hsp90α interaction facilitates the nuclear transport of viral tegument protein VP16, the core factor initiating the expression of HSV-1 IE genes. The transcription factor YY1 mediates the induction of MAMDC2-AS1 upon HSV-1 infection. Our study elucidates the contribution of lncRNA to HSV-1 infection susceptibility in human cells and the role of Hsp90α RNA binding activity in HSV-1 infection.
- Subjects :
- Hsp90α
viruses
Active Transport, Cell Nucleus
RNA-binding protein
Herpesvirus 1, Human
MAMDC2-AS1
nuclear transport
Biology
Applied Microbiology and Biotechnology
Cell Line
03 medical and health sciences
Transcription (biology)
Gene expression
Humans
Gene silencing
HSP90 Heat-Shock Proteins
RNA-Seq
single-cell RNA-sequencing
Genes, Immediate-Early
Molecular Biology
Transcription factor
Gene
YY1 Transcription Factor
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
Cell Nucleus
0303 health sciences
RNA-Binding Proteins
RNA
Herpes Simplex Virus Protein Vmw65
Cell Biology
HSV-1
tegument protein
Cell biology
RNA, Long Noncoding
Ectopic expression
Single-Cell Analysis
Research Paper
Developmental Biology
Subjects
Details
- ISSN :
- 14492288
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Sciences
- Accession number :
- edsair.doi.dedup.....c44811f8d90f1d86885e518c898000d2