Dataset Information

Detecting virus-specific effects on post-infection temporal gene expression.

ABSTRACT: BACKGROUND:Different types of viruses have different envelope proteins, and may have their shared or distinctive host-virus interactions which result in various post-infection effects in humans and animals. These effects often do not appear at once but take time to unfold. To characterize the virus-specific effects, we applied a Multivariate Polynomial Time-dependent Genetic Association (MPTGA) method, previously proposed for detecting differences in temporal gene expression traits, to test for the differences in mouse lung transcriptome response to infection of different subtypes of influenza A viruses. RESULTS:We compared two methods: the Multivariate Polynomial Time-dependent Genetic Association (MPTGA) method, and the conventional modified t-test, to study the virus-specific effects on mouse lung gene expression. Both methods found H3N2 to be the most different virus among the three viruses tested, with the largest number of genes with H3N2-specific effects. However, the MPTGA method demonstrated much higher power of detection, and the detected genes with virus-specific effects showed better biological relevance. CONCLUSIONS:Transcriptome response to virus infection is dynamic. MPTGA which leverages temporal gene expression traits showed increased power in detecting biologically relevant virus-specific effects comparing with conventional t-test method.

SUBMITTER: Chen Q

PROVIDER: S-EPMC6439963 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Detecting virus-specific effects on post-infection temporal gene expression.

Chen Quan Q Zhu Jun J

BMC bioinformatics 20190329 Suppl 3

<h4>Background</h4>Different types of viruses have different envelope proteins, and may have their shared or distinctive host-virus interactions which result in various post-infection effects in humans and animals. These effects often do not appear at once but take time to unfold. To characterize the virus-specific effects, we applied a Multivariate Polynomial Time-dependent Genetic Association (MPTGA) method, previously proposed for detecting differences in temporal gene expression traits, to t ...[more]

PMID: 30925863

Similar Datasets

Project description:UnlabelledEbola virus (EBOV) causes a severe hemorrhagic fever with a deficient immune response, lymphopenia, and lymphocyte apoptosis. Dendritic cells (DC), which trigger the adaptive response, do not mature despite EBOV infection. We recently demonstrated that DC maturation is unblocked by disabling the innate response antagonizing domains (IRADs) in EBOV VP35 and VP24 by the mutations R312A and K142A, respectively. Here we analyzed the effects of VP35 and VP24 with the IRADs disabled on global gene expression in human DC. Human monocyte-derived DC were infected by wild-type (wt) EBOV or EBOVs carrying the mutation in VP35 (EBOV/VP35m), VP24 (EBOV/VP24m), or both (EBOV/VP35m/VP24m). Global gene expression at 8 and 24 h was analyzed by deep sequencing, and the expression of interferon (IFN) subtypes up to 5 days postinfection was analyzed by quantitative reverse transcription-PCR (qRT-PCR). wt EBOV induced a weak global gene expression response, including markers of DC maturation, cytokines, chemokines, chemokine receptors, and multiple IFNs. The VP35 mutation unblocked the expression, resulting in a dramatic increase in expression of these transcripts at 8 and 24 h. Surprisingly, DC infected with EBOV/VP24m expressed lower levels of many of these transcripts at 8 h after infection, compared to wt EBOV. In contrast, at 24 h, expression of the transcripts increased in DC infected with any of the three mutants, compared to wt EBOV. Moreover, sets of genes affected by the two mutations only partially overlapped. Pathway analysis demonstrated that the VP35 mutation unblocked pathways involved in antigen processing and presentation and IFN signaling. These data suggest that EBOV IRADs have profound effects on the host adaptive immune response through massive transcriptional downregulation of DC.ImportanceThis study shows that infection of DC with EBOV, but not its mutant forms with the VP35 IRAD and/or VP24 IRAD disabled, causes a global block in expression of host genes. The temporal effects of mutations disrupting the two IRADs differ, and the lists of affected genes only partially overlap such that VP35 and VP24 IRADs each have profound effects on antigen presentation by exposed DC. The global modulation of DC gene expression and the resulting lack of their maturation represent a major mechanism by which EBOV disables the T cell response and suggests that these suppressive pathways are a therapeutic target that may unleash the T cell responses during EBOV infection.

Project description:After viral infection, the virus relies on the host cell's complex metabolic and biosynthetic machinery for replication. However, the impact of avian influenza virus (AIV) on metabolites and gene expression in poultry cells remains unclear. To investigate this, we infected chicken embryo fibroblasts DF1 cells with H9N2 AIV at an MOI of 3. Our aim was to explore how H9N2 AIV alters DF1 cells metabolic pathways to facilitate its replication. We employed metabolomics and transcriptomics techniques to analyze changes in metabolite content and gene expression. Metabolomics analysis revealed a significant increase in glutathione-related metabolites, including reduced glutathione (GSH), oxidized glutathione (GSSG) and total glutathione (T-GSH) upon H9N2 AIV infection in DF1 cells. Elisa results confirmed elevated levels of GSH, GSSG, and T-GSH consistent with metabolomics findings, noting a pronounced increase in GSSG compared to GSH. Transcriptomics showed significant alterations in genes involved in glutathione synthesis and metabolism post-H9N2 infection. However, adding the glutathione synthesis inhibitor BSO exogenously significantly promoted H9N2 replication in DF1 cells. This was accompanied by increased mRNA levels of pro-inflammatory cytokines (IL-1β, IFN-γ) and decreased mRNA levels of anti-inflammatory cytokines (TGF-β, IL-13). BSO also reduced catalase (CAT) gene expression and inhibited its activity, leading to higher reactive oxygen species (ROS) and malondialdehyde (MDA) level in DF1 cells. qPCR results indicated decreased mRNA levels of Nrf2, NQO1, and HO-1 with BSO, ultimately increasing oxidative stress in DF1 cells. Therefore, the above results indicated that H9N2 AIV infection in DF1 cells activated the glutathione metabolic pathway to enhance the cell's self-defense mechanism against H9N2 replication. However, when GSH synthesis is inhibited within the cells, it leads to an elevated oxidative stress level, thereby promoting H9N2 replication within the cells through Nrf2/HO-1 pathway. This study provides a theoretical basis for future rational utilization of the glutathione metabolic pathway to prevent viral replication.

Dataset Information

Detecting virus-specific effects on post-infection temporal gene expression.

Publications

Detecting virus-specific effects on post-infection temporal gene expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets