Human cytomegalovirus antigen presentation by HLA-G in infected cells
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ABSTRACT:
PROVIDER: PRJEB84051 | ENA |
REPOSITORIES: ENA
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Project description:Placental infection plays a central role in the pathogenesis of congenital human cytomegalovirus (HCMV) infections and is a cause of fetal growth restriction and pregnancy loss. HCMV can replicate in some trophoblast cell types, but it remains unclear how the virus evades antiviral immunity in the placenta and how infection compromises placental development and function. Human trophoblast stem cells (TSCs) can be differentiated into extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs). This study assessed the utility of TSCs as a model of HCMV infection in the first trimester placenta. TSCs and TSC-derived EVTs and STBs were infected with HCMV (TB40/Ewt-mCherry). RNA was isolated from infected cells at 24, 48, and 72 hours post-infection and Illumina RNA-Sequencing was used to measure viral and host gene expression. Viral gene expression in TSCs does not follow the kinetic patterns observed during lytic infection in fibroblasts. Canonical antiviral responses were largely not observed in HCMV-infected TSCs and TSC-derived trophoblasts. Rather, infection dysregulated factors involved in cell identity, differentiation, and WNT signaling.
2023-12-14 | GSE248772 | GEO
Project description:Human cytomegalovirus (HCMV) is a common herpesvirus that persistently infects a large portion of the world's population. Despite the robust host immune response, HCMV is able to replicate, evade host defenses, and establish latency throughout the lifespan by developing multiple immunomodulatory strategies, making the studies on the interaction between HCMV infection and host response particularly important. HCMV has a strict host specificity that specifically infects humans. Therefore, most of the in vivo researches of HCMV rely on clinical samples. Fortunately, the establishment of humanized mouse models allows for convenient in-lab animal experiments involving HCMV infection. Single-cell RNA sequencing(scRNA-seq) enables the study of the relationship between viral and host gene expressions at the single-cell level within host cells. In this study, we assessed the gene expression alterations of PBMCs at the single-cell level within HCMV-infected humanized mice, which sheds light onto the virus-host interactions in the context of HCMV infecton of humanized mice and provides a valuable dataset for the related researches.
2024-05-20 | GSE267869 | GEO
Project description:We have established that human cytomegalovirus (HCMV) infection modulates the biology of target primary blood monocytes, allowing HCMV to use monocytes as 'vehicles' for its systemic spread. HCMV infection of monocytes results in rapid induction of PI(3)K and NF-kB activity. Integrins, which are upstream of the PI(3)K and NF-kB pathways, were shown to be involved in HCMV binding to and entry into fibroblasts, suggesting that receptor-ligand-mediated signaling following viral binding to integrins on monocytes could trigger the functional changes seen in infected monocytes. We now show that integrin engagement and the activation of the integrin/Src-signaling pathway is essential for the induction of HCMV-infected monocyte motility. To investigate how integrin engagement by HCMV triggers monocyte motility, we examined the infected monocyte transcriptome and found that the integrin/Src-signaling pathway regulates the expression of paxillin, which is an important signal transducer in the regulation of actin rearrangement during cell adhesion and movement. Functionally, we observed that paxillin is activated via the integrin/Src-signaling pathway and is required for monocyte motility. Because motility is intimately connected to cellular cytoskeletal organization, a process that is also important in viral entry, we investigated the role paxillin regulation plays in the process of viral entry of monocytes. New results confirmed that HCMV`s ability to enter target monocytes is significantly inhibited in cells deficient in paxillin expression or that had their integrin/Src/paxillin signaling pathway blocked. From our data, HCMV-cell interactions emerge as an essential trigger for the cellular changes that allow for HCMV entry and hematogenous dissemination. Monocytes were mock-infected, HCMV-infected, or pretreated with PP2 inhibitor prior to HCMV infection. There were three samples analyzed per individual replicate. Three replicates are included. comparative studies with a use of the specific Src kinase activity inhibitor
2010-10-31 | E-GEOD-24238 | biostudies-arrayexpress
Project description:Natural killer (NK) cells play a dual role in the defense against viral pathogens by directly lysing infected cells as well as by regulating anti-viral T cell immunity. Infection by human cytomegalovirus (HCMV) promotes a persistent expansion of NKG2C+ adaptive NK cells which have been shown to display enhanced antibody-dependent responses against infected targets and associated to viral control in transplanted patients. Based on gene expression data showing increased transcription of CIITA and several genes related to the MHC class II pathway in adaptive NK cells, we explored their putative capacity for antigen presentation to CD4+ T cells. Phenotypic analysis confirmed a preferential steady-state expression of HLA-DR by circulating NKG2C+ adaptive NK cells in healthy individuals. Expression of HLA-DR in NKG2C+ adaptive NK cells was variable and unrelated to the expression of activation (i.e., CD69 and CD25) or differentiation (i.e., FcRγ chain, CD57) markers, remaining stable over time at the individual level. Incubation of purified NK cells with HCMV complexed with serum specific antibodies induced an up-regulation of surface HLA-DR concomitant to CD16 loss whereas no changes in CD80/CD86 co-stimulatory ligands were detected. In addition, surface CX3CR1 decreased upon antigen-loading while HLA-DR+ NK cells maintained a CCR7-, CXCR3low homing profile. Remarkably, HCMV-loaded purified NK cells activated autologous CD4+ T cells in an HLA-DR dependent manner. The fraction of T lymphocytes activated by antigen-loaded NK cells was smaller than that stimulated by monocyte-derived dendritic cells, corresponding to CD28-negative effector-memory CD4+ T cells with cytotoxic potential. Antigen presentation by NK cells activated a polyfunctional CD4+ T cell response characterized by degranulation (CD107a) and the secretion of Th1 cytokines (IFNγ and TNFα). Overall, our data discloses the capacity of NKG2C+ adaptive NK cells to process and present HCMV antigens to memory CD4+ cytotoxic T cells, directly regulating their response to the viral infection.
| S-EPMC6456717 | biostudies-literature
Project description:We report the application of RNA sequencing for transcriptome analysis of HCMV infected Human nasal turbinate tissues, enabling the study of tissue responses to HCMV infection
2020-07-16 | GSE152114 | GEO
Project description:We have established that human cytomegalovirus (HCMV) infection modulates the biology of target primary blood monocytes, allowing HCMV to use monocytes as “vehicles” for its systemic spread. HCMV infection of monocytes results in rapid induction of PI(3)K and NF-κB activity. Integrins, which are upstream of the PI(3)K and NF-κB pathways, were shown to be involved in HCMV binding to and entry into fibroblasts, suggesting that receptor-ligand-mediated signaling following viral binding to integrins on monocytes could trigger the functional changes seen in infected monocytes. We now show that integrin engagement and the activation of the integrin/Src-signaling pathway is essential for the induction of HCMV-infected monocyte motility. To investigate how integrin engagement by HCMV triggers monocyte motility, we examined the infected monocyte transcriptome and found that the integrin/Src-signaling pathway regulates the expression of paxillin, which is an important signal transducer in the regulation of actin rearrangement during cell adhesion and movement. Functionally, we observed that paxillin is activated via the integrin/Src-signaling pathway and is required for monocyte motility. Because motility is intimately connected to cellular cytoskeletal organization, a process that is also important in viral entry, we investigated the role paxillin regulation plays in the process of viral entry of monocytes. New results confirmed that HCMV`s ability to enter target monocytes is significantly inhibited in cells deficient in paxillin expression or that had their integrin/Src/paxillin signaling pathway blocked. From our data, HCMV-cell interactions emerge as an essential trigger for the cellular changes that allow for HCMV entry and hematogenous dissemination.
2010-10-31 | GSE24238 | GEO
Project description:RNA2.7 is a long non-coding RNA encoded by HCMV, which has be reported related with apoptosis. We have found RNA2.7 can also affect virus replication. We used the microarrays to look for HCMV RNA2.7 related host transcripts. We infected HELF cells by HCMV BAC HAN which was contructed from a HCMV clinical isolate, and BAC HAN^RNA2.7 which was a mutant of BAC HAN by deletion of RNA2.7. By running microarray and bioanalysis, we aimed to find RNA2.7 involvement in host and virus replication and transcription.
2016-03-01 | E-GEOD-73954 | biostudies-arrayexpress
Project description:Human cytomegalovirus (HCMV) has profound effect on gene expression during infection of monocytes. We performed RNA-seq and RIBO-seq to analyze the extend to which HCMV reshapes the transciptome and translatome of infected monocytes.
2024-01-10 | GSE248927 | GEO
Project description:RNA2.7 is a long non-coding RNA encoded by HCMV, which has be reported related with apoptosis. We have found RNA2.7 can also affect virus replication. We used the microarrays to look for HCMV RNA2.7 related host transcripts.
2016-03-01 | GSE73954 | GEO
Project description:In this study, RNA-seq analysis was performed to generally understand the circRNA profiles of mock-infected and HCMV-infected HELF cells. Totally, 27,409 and 35,515 host circRNAs were identified in mock-infected and HCMV-infected HELF cells by RNA-seq respectively. Among them, 278 circRNAs were significantly modified filtrating by a threshold value of >2 (or <-2) fold-change and q-value <0.05. GO and KEGG pathway enrichment analysis suggested that the remarkably changed circRNAs might play important roles in viral entry, cell proliferation, and inhibition of apoptosis. Verification of four selected circRNAs ( circSP100, circMAP3K1, circTRIO, and circPLEKHM1) was performed using RT-PCR and Sanger sequencing. Moreover, further verification of circSP100 was performed using northern blotting and RT-qPCR and proteins binding directly to circSP100 were purified using RNA antisense purification (RAP).
2020-09-05 | GSE138836 | GEO