Project description:The goal of this study was to compare the whole transcriptional profile (RNA-seq) of herpes simplex virus type 1 (HSV-1) infected and mock infected human fibroblast KMB17 strain at 48 hours post infection.There is increasing evidence that circular RNAs (circRNAs) are involved in diverse pathogenesis processes; however, their roles in virus infection remain unclear. Here, we profiled global changes of circRNAs, genes and microRNA (miRNAs) under herpes simplex virus type 1 (HSV-1) infection by RNA-seq. Numerous dysregulated transcripts comprised of 536 circRNAs, 3,885 genes and 207 miRNAs were found during viral infection. The dysregulated genes were enriched to NOD-like receptor signaling pathway, Jak-STAT signaling pathway and pathways of apoptosis, cell cycle progression and cell death, all of which may be implicated in viral pathogenesis and cellular immunity. Further integration analysis of circRNAs, genes and miRNAs reveals putative involvement of circRNAs in viral pathogenesis and antiviral immunity by circRNA-miRNA-gene regulatory axis. This work provides a comprehensive view for dysregulated circRNAs induced by HSV-1 and their interplay with miRNAs and genes, thus offering new insights into the mechanisms of interactions between HSV-1 and its host.
Project description:We show that Herpes simplex virus 1 (HSV-1) induces the expression of about 1000 antisense transcripts from the human host cell genome.
Project description:The goal of the study was to determine whether low dose HDACi sensitizes human malignant meningioma cells to the cytotoxic capacity of oncolytic herpes simplex virus G47delta. RNA sequencing was used to examine transcriptomic changes mediated by HDACi preexposure before oncolytic virus infection.
Project description:This is a part of the study that shows that a host gene,ONECUT2 (OC2), promote herpes simplex virus 1 (HSV-1) transcription. These RNA-seq analyses viral genes transcription in Neuro-2a cells. Neuro-2a cells were transfected with pOC2△HOX2 and pcDNA plasmids for 42 hours then infected with herpes simple virus1 for 5 hours.
Project description:Herpes simplex virus mutants lacking the vhs gene are severely attenuated in animal models of pathogenesis and exhibit reduced growth in primary cell culture. As a result of these properties vhs-deleted virus have been proposed as live-attenuated viruses. Despite these findings and their implications for vacccines, the mechanisms by which vhs promotes infection in cell culture and in vivo are not understood. In this study we demonstrate that vhs-deficent viruses replicate to reduced levels in interferon(IFN)- primed cells. Furthermore, vhs-defective viruses induce increased levels of IFN? and IFN?-stimulated genes, and increased levels of eIF2? phosphorylation in infected cells. In addition, we demonstrate a generalized over-expression of viral RNAs following infection with a vhs-deficient virus. This suggests increased expression of IFN pathway inducing double stranded RNA, a potent pathogen-associated molecular pattern (PAMP). Together these data show that vhs likely functions to reduce innate immune responses and thereby acts as critical determinant of viral pathogenesis. Keywords: time course, genetic modification Time course (1,3,6,9 & 12h) of HSV infected mouse embryo fibroblasts. Wild type (KOS) virus is co-hybridized with vhs null virus (NHB). Each time-point is hybridized in quadruplicate.
Project description:DDX3X is a mammalian RNA helicase that regulates RNA metabolism, cancers, innate immunity and several RNA viruses. We discovered that herpes simplex virus 1, a nuclear DNA replicating virus, highjacks redirects DDX3X to the nuclear envelope where it surprisingly modulates the exit of newly assembled viral particles. DDX3X depletion also led to an accumulation of virions in intranuclear herniations. Mechanistically, we show that DDX3X physically and functionally interacts with the virally encoded nuclear egress complex at the inner nuclear membrane. DDX3X also bound to and stimulated the incorporation in mature particles of pUs3, a herpes kinase that promotes viral nuclear release across the outer nuclear membrane. Overall, the data highlights two unexpected roles for an RNA helicase during the passage of herpes simplex viral particles through the nuclear envelope. This reveals a highly complex interaction between DDX3X and viruses and provides new opportunities to target viral propagation.
Project description:This is a part of the study that shows that a host gene,ONECUT2( OC2), promotes herpes simplex virus 1 (HSV-1) genome accessibility. These ATAC analyses are for viral and host genome accessibility in Neuro-2a cells. Neuro-2a cells were transfected with pOC2△HOX2 and pcDNA plasmids for 42 hours then infected with herpes simple virus1 for 2 hours.
Project description:Herpes simplex virus type-1 (HSV-1) is wide-spread dsDNA virus that establishes life-long latency and causes diverse severity of symptoms. In this study, HEK 293T cells with low Toll-like receptor (TLR) and Stimulator of interferon genes protein (STING) expression was infected with HSV-1 and subjected to quantitative proteomic analysis. By using a subcellular fractionation strategy and high-performance mass spectrometry, a total of 5,982 host proteins were quantified, of which 484 proteins were differentially regulated. Bioinformatics analysis indicated that multiple signaling pathways were involved in HSV-1 infection.