Functional single-cell genomics of human cytomegalovirus infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA693896 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13501500.fastq.gz | Fastqsanger.gz | |||
| SRR13501501.fastq.gz | Fastqsanger.gz | |||
| SRR13501502.fastq.gz | Fastqsanger.gz | |||
| SRR13501503.fastq.gz | Fastqsanger.gz | |||
| SRR13501504.fastq.gz | Fastqsanger.gz |
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Project description:The overall goal of the study was to use in vivo data combined with functional genomics to define gene expression signatures representative of a spectrum of HSV CNS infections. Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and Δvhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1(-/-)) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (Δvhs infection of control mice), neurological disease followed by viral clearance (Δvhs infection of Stat1(-/-) mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1(-/-) mice). Through the use of functional genomics on the infected brain stem and liver, we determined gene signatures that were representative of the three infection outcomes.
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Project description:Porcine cytomegalovirus (PCMV) is a member of the genus Cytomegalovirus, subfamily Betaherpesvirinae, and family Herpesvirus. PCMV is a major immunosuppressive virus that mainly suppress the immune function of T lymphocytes and macrophages. PCMV is widely distributed all over the world, but there are not significantly different serotypes found. Moreover, the molecular mechanisms of host anti-PCMV infection and the molecular immunosuppressive mechanisms of PCMV is still not well charaterized. To understand the PCMV potential impact on the function of immune organs, we performed microarray assay to analyze the transcriptome of porcine immune organs after PCMV infection. We identified 5582 differential expression genes by PCMV infection in microarray. There are 2161 upregulated genes and 3421 down-regulated by PCMV infection genes compare to the uninfected control group. We confirmed 13 differentially expressed immune-related genes by quantitative real-time RT-PCR (qPCR). Gene ontology, gene interaction networks and KEGG pathway analysis uncovered the differentially expressed genes interaction regulatory network. These findings indicated that PCMV regulates multiple functional pathways, including immune system process, cellular process, metabolic process, networks of cytokine-cytokine receptor interaction, TGF-beta signaling pathway, lymphocytes receptor signaling pathway and TNF signaling pathway. Our study is the first comprehensive attempt to explore the host transcriptional response to PCMV infection in porcine immune systems. It provided new insights into the immunosuppressive molecular mechanisms and pathogenesis of PCMV. This previously unrecognized endogenous antiviral mechanism has implications for development of host-directed strategies to the prevention and treatment of immunosuppressive viral diseases.
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