Peste des Petits Ruminants Virus Attachment and Entry into Caprine Endometrial Epithelial Cells Profoundly Effects Early Cellular Gene Expression
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ABSTRACT:
ORGANISM(S): Capra hircus Ovis aries
PROVIDER: GSE85204 | GEO | 2018/02/14
REPOSITORIES: GEO
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Project description:Peste des petits ruminants virus (PPRV), the etiological agent of peste des petits ruminants (PPR), causes an acute or subacute disease in small ruminants. Although abortion is observed in an unusually large proportion of pregnant goats during outbreaks of PPR, the pathogenic mechanism underlying remains unclear. Here, the gene expression profile of caprine endometrial epithelial cells (EECs) infected with PPRV Nigeria 75/1 was determined by DNA microarray to investigate the cellular response immediately after viral entry. The microarray analysis revealed that a total of 146 genes were significantly dysregulated by PPRV internalization within 1 h post-infection (hpi). Of these, 85 genes were upregulated and 61 genes were downregulated. Most of these genes, including NFKB1A, JUNB, and IL1A, have not previously been reported in association with PPRV infection in goats. Following viral replication (24 hpi), the expression of 307 genes were significantly upregulated and that of 261 genes were downregulated. The data for the genes differentially expressed in EECs were subjected to a time sequence profile analysis, gene network analysis and pathway analysis. The gene network analysis showed that 13 genes (EIF2AK3, IL10, TLR4, ZO3, NFKBIB, RAC1, HSP90AA1, SMAD7, ARG2, JUNB, ZFP36, APP, and IL1A) were located in the core of the network. We clearly demonstrate that PPRV infection upregulates the expression of nectin-4 after 1 hpi, which peaked at 24 hpi in EECs. In conclusion, this study demonstrates the early cellular gene expression in the caprine endometrial epithelial cells after the binding and entry of PPRV.
| S-EPMC5784595 | biostudies-literature
Project description:We have used RNA-Seq to examine lymphocytes and monocytes expression profiles in goats infected with PPRV (Izatnagar94), suggesting its important functions in immune response during virus infection.
2020-04-10 | GSE132429 | GEO
Project description:Peste des petits ruminants virus (PPRV) is a negative-stranded RNA virus belonging to the Paramyxoviridae family and causes acute, highly contagious disease in small ruminants. Lysine acetylation plays central role in regulating gene expression. However, the extent and function of lysine acetylation in host cells during PPRV infection remains unknown. In this study, intensive proteomic quantification analysis of the proteome and acetylome of PPRV-infected Vero cells was performed using dimethylation labeling-based quantitative proteomics. As results, we identified 4729 proteins and 1068 acetylated proteins with 2641 quantified modification sites detected by mass spectrometry, of which 304 acetylated proteins with 410 acetylation sites were significantly acetylated in response to PPRV infection. Bioinformatics analyses revealed that the differentially acetylated proteins participated in carbohydrate catabolic and DNA metabolic process, and were associated with multifarious functions, suggesting that intracellular activities were extensively changed after PPRV infection. Protein-protein interaction network of the identified proteins further indicated that a variety of chaperone and ribosome processes were modulated by acetylation. To our knowledge, this is the first study on acetylome in host cell infected with PPRV. It provides an important point for future studies on the acetylated proteins involved in the host response to PPRV replication.
2023-10-24 | PXD025081 | Pride
Project description:Peste des petits ruminants virus (PPRV) infection causes highly contagious and severe disease in domestic and wild ruminants. It is widely reported that PRRV infection causes considerable innate immunosuppression in its host and promotes viral replication. However, how does the host rescue the innate immune response to counteract this immunosuppression during viral replication is poorly understood. The goat fetal fibroblasts (GFFs) have been commonly used as host-original cells to investigate the pathogenesis of PPRV. To explore the mechanisms of how host counteracts PPRV-mediated innate immunosuppression, a high-throughput quantitation proteomic approach (iTRAQ in conjunction with LC-MS/MS) was used to investigate the proteome landscape of GFFs in response to PPRV infection. Eventually, the proteomic analysis gained 497 up-regulated proteins and 358 down-regulated proteins (PPRV-infected cells versus mock-infected cells). The complement and coagulation cascades, protein digestion and absorption, and cytokine-cytokine receptor interaction pathways were significantly regulated in response to PPRV infection. ErmineJ analysis of the differentially expressed proteins (DEPs) identified the significantly enriched GO categories for response to interferon-gamma and positive regulation of ERK1 and ERK2 cascade. In addition, many immune related proteins, such as interferon gamma, 2'-5'-oligoadenylate synthase-like protein, toll-like receptor 9, toll-like receptor 6, NOD1, plasminogen activator inhibitor 1, and Wnt-5a were significantly upregulated. This suggested that the innate immune response was triggered during PPRV infection in GFFs. We subsequently identified that the E3 ubiquitin ligase FANCL was critically involved in regulation of the innate immune response during PPRV infection. FANCL inhibited PPRV infection by enhancing type I interferon (IFN) and interferon-stimulated genes (ISGs) expression. Further study indicated that FANCL induced type I IFN production by promoting TBK1 phosphorylation, and therefore impairing PPRV-mediated immunosuppression and revealing an antiviral function against PPRV.
2021-07-26 | PXD022271 | Pride
Project description:Peste des Petits Ruminants (PPR) is a highly infectious disease caused by a virus of the genus Morbillivirus (PPRV), infecting mainly sheep and goat. Susceptibility of host can vary widely with host breed and virus strain. The mechanisms underlying this variability are not well understood. Here, we carried out the first comparative in vitro study on goat peripheral blood mononuclear cells (PBMCs) infected with PPRV strains of different virulence, vaccine strain (N75/1), low- (IC89), and high-virulent strain (MA08). Goat PBMCs were infected by the different strains and stimulated with Concanavalin A (Con A), and proteome changes of these cells were evaluated during the infection. The level of PPRV replication was assessed first by RT-qPCR quantification of viral N mRNA and by labelling the viral N protein inside the cells with specific antibodies and analysed by flow cytometry. The dynamics of PBMC sub-populations were also evaluated by flow cytometry. Our results showed that viral replication is critical for PPRV inhibitory effect on PBMCs proliferation. Highly virulent MA08 strain reached a higher level of replication in ConA-stimulated PBMCs and induced higher mortality compared to other strains. Low-virulent IC89 strain showed the lower replication level and cell proliferative inhibitory capacities. Differences in immune genes expression levels were assessed using RNAseq analysis and protein expression was compared using mass spectrometry. Analysis of these data provided the transcriptional and proteome landscape of PBMCs infected with these strains. The possible association between the transcriptional and proteome landscape and changes in immune cell subpopulations dynamics was explored.
2021-11-03 | PXD024890 | Pride
Project description:Stress granules (SGs) formation is a conserved cellular strategy to reduce stress-related damage regulating cell survival. A Mass spectrometry-based profiling of the interactome of PPRV N protein revealed that PPRV N interacted with PACT to regulate the assembly of SGs. N protein inhibited the interaction between PACT and a PKR inhibitor TRBP through binding to the M1 domain of PACT, which enhanced the interaction between PACT and PKR and thus promoted PKR activation and subsequent eIF2α phosphorylation as well as SGs formation. The regulatory function of N protein was strikingly abrogated in PACT-/- cells. PPRV infection-induced SGs through the PKR/eIF2α pathway are PACT-dependent. The loss of function assay indicated that PPRV-induced SGs were critical for PPRV replication. We concluded that the PPRV N protein manipulates the host PKR/eIF2α/SGs axis to favor virus replication.
2022-12-27 | PXD039104 |
Project description:Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP(1,2)) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP(1,2) (VLP(VP40-GP)) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLP(VP40) (particles lacking GP(1,2)) caused an aberrant response. This suggests that GP(1,2) binding to macrophages plays an important role in the immediate cellular response.
| S-EPMC3196478 | biostudies-literature
Project description:The mitochondrial antiviral-signaling protein (MAVS, also known as VISA, IPS-1, or CARDIF) plays an essential role in the type I interferon (IFN) response and in retinoic acid-inducible gene I (RIG-I) mediated antiviral innate immunity in mammals. In this study, the caprine MAVS gene (caMAVS, 1566 bp) was identified and cloned. The caMAVS shares the highest amino acid similarity (98.1%) with the predicted sheep MAVS. Confocal microscopy analysis of partial deletion mutants of caMAVS revealed that the transmembrane and the so-called Non-Characterized domains are indispensable for intracellular localization to mitochondria. Overexpression of caMAVS in caprine endometrial epithelial cells up-regulated the mRNA levels of caprine interferon-stimulated genes. We concluded that caprine MAVS mediates the activation of the type I IFN pathway. We further demonstrated that both the CARD-like domain and the transmembrane domain of caMAVS were essential for the activation of the IFN-β promotor. The interaction between caMAVS and caprine RIG-I and the vital role of the CARD and NC domain in this interaction was demonstrated by co-immunoprecipitation. Upon infection with the Peste des Petits Ruminants Virus (PPRV, genus Morbillivirus), the level of MAVS was greatly reduced. This reduction was prevented by the addition of the proteasome inhibitor MG132. Moreover, we found that viral protein V could interact and colocalize with MAVS. Together, we identified caMAVS as a RIG-I interactive protein involved in the activation of type I IFN pathways in caprine cells and as a target for PPRV immune evasion.
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Project description:Peste des petits ruminants virus causes a highly infectious disease of small ruminants that is endemic across Africa, the Middle East and large regions of Asia. The virus is considered to be a major obstacle to the development of sustainable agriculture across the developing world and has recently been targeted by the World Organisation for Animal Health (OIE) and the Food and Agriculture Organisation (FAO) for eradication with the aim of global elimination of the disease by 2030. Fundamentally, the vaccines required to successfully achieve this goal are currently available, but the availability of novel vaccine preparations to also fulfill the requisite for differentiation between infected and vaccinated animals (DIVA) may reduce the time taken and the financial costs of serological surveillance in the later stages of any eradication campaign. Here, we overview what is currently known about the virus, with reference to its origin, updated global circulation, molecular evolution, diagnostic tools and vaccines currently available to combat the disease. Further, we comment on recent developments in our knowledge of various recombinant vaccines and on the potential for the development of novel multivalent vaccines for small ruminants.
| S-EPMC4655833 | biostudies-literature
Project description:Peste des Petits Ruminants virus N gene partial sequences
| PRJNA801092 | ENA