Dataset Information

Proteomic Analysis Uncovers Measles Virus Protein C Interaction With p65-iASPP Protein Complex.

ABSTRACT: Viruses manipulate the central machineries of host cells to their advantage. They prevent host cell antiviral responses to create a favorable environment for their survival and propagation. Measles virus (MV) encodes two nonstructural proteins MV-V and MV-C known to counteract the host interferon response and to regulate cell death pathways. Several molecular mechanisms underlining MV-V regulation of innate immunity and cell death pathways have been proposed, whereas MV-C host-interacting proteins are less studied. We suggest that some cellular factors that are controlled by MV-C protein during viral replication could be components of innate immunity and the cell death pathways. To determine which host factors are targeted by MV-C, we captured both direct and indirect host-interacting proteins of MV-C protein. For this, we used a strategy based on recombinant viruses expressing tagged viral proteins followed by affinity purification and a bottom-up mass spectrometry analysis. From the list of host proteins specifically interacting with MV-C protein in different cell lines, we selected the host targets that belong to immunity and cell death pathways for further validation. Direct protein interaction partners of MV-C were determined by applying protein complementation assay and the bioluminescence resonance energy transfer approach. As a result, we found that MV-C protein specifically interacts with p65-iASPP protein complex that controls both cell death and innate immunity pathways and evaluated the significance of these host factors on virus replication.

SUBMITTER: Meignie A

PROVIDER: S-EPMC7950213 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Proteomic Analysis Uncovers Measles Virus Protein C Interaction With p65-iASPP Protein Complex.

Meignié Alice A Combredet Chantal C Santolini Marc M Kovács István A IA Douché Thibaut T Gianetto Quentin Giai QG Eun Hyeju H Matondo Mariette M Jacob Yves Y Grailhe Regis R Tangy Frédéric F Komarova Anastassia V AV

Molecular & cellular proteomics : MCP 20210127

Viruses manipulate the central machineries of host cells to their advantage. They prevent host cell antiviral responses to create a favorable environment for their survival and propagation. Measles virus (MV) encodes two nonstructural proteins MV-V and MV-C known to counteract the host interferon response and to regulate cell death pathways. Several molecular mechanisms underlining MV-V regulation of innate immunity and cell death pathways have been proposed, whereas MV-C host-interacting protei ...[more]

PMID: 33515806

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Project description:The hemagglutinin (H) protein of measles virus (MeV) interacts with a cellular receptor which constitutes the initial stage of infection. Binding of H to this host cell receptor subsequently triggers the F protein to activate fusion between virus and host plasma membranes. The search for MeV receptors began with vaccine/laboratory virus strains and evolved to more relevant receptors used by wild-type MeV. Vaccine or laboratory strains of measles virus have been adapted to grow in common cell lines such as Vero and HeLa cells, and were found to use membrane cofactor protein (CD46) as a receptor. CD46 is a regulator that normally prevents cells from complement-mediated self-destruction, and is found on the surface of all human cells, with the exception of erythrocytes. Mutations in the H protein, which occur during adaptation and allow the virus to use CD46 as a receptor, have been identified. Wild-type isolates of measles virus cannot use the CD46 receptor. However, both vaccine/laboratory and wild-type strains can use an immune cell receptor called signaling lymphocyte activation molecule family member 1 (SLAMF1; also called CD150) and a recently discovered epithelial receptor known as Nectin-4. SLAMF1 is found on activated B, T, dendritic, and monocyte cells, and is the initial target for infections by measles virus. Nectin-4 is an adherens junction protein found at the basal surfaces of many polarized epithelial cells, including those of the airways. It is also over-expressed on the apical and basal surfaces of many adenocarcinomas, and is a cancer marker for metastasis and tumor survival. Nectin-4 is a secondary exit receptor which allows measles virus to replicate and amplify in the airways, where the virus is expelled from the body in aerosol droplets. The amino acid residues of H protein that are involved in binding to each of the receptors have been identified through X-ray crystallography and site-specific mutagenesis. Recombinant measles "blind" to each of these receptors have been constructed, allowing the virus to selectively infect receptor specific cell lines. Finally, the observations that SLAMF1 is found on lymphomas and that Nectin-4 is expressed on the cell surfaces of many adenocarcinomas highlight the potential of measles virus for oncolytic therapy. Although CD46 is also upregulated on many tumors, it is less useful as a target for cancer therapy, since normal human cells express this protein on their surfaces.

Project description:ObjectiveThe identification of depression primarily relies on the clinical symptoms and psychiatric evaluation of the patient, in the absence of objective and quantifiable biomarkers within clinical settings. This study aimed to explore potential serum biomarkers associated with depression.MethodsSerum samples from a training group comprising 48 depression patients and 48 healthy controls underwent proteomic analysis. Magnetic bead-based weak cation exchange (MB-WCX) and MALDI-TOF-MS were used in combination. To screen the differential peaks, ClinProTools software was employed. The proteins were identified using LC-MS/MS. ELISA was employed to confirm the expression of entire protein in the serum of the verification cohort, which encompassed 48 individuals who had been diagnosed with Depression and 48 healthy controls who were collected prospectively. Subsequently, logistic regression analysis was conducted to determine the diagnostic efficacy of the aforementioned predictors.ResultsFive potential biomarker peaks indicating depression were identified in serum samples (peak 1, m/z: 1868.21; peak 2, m/z: 1062.35; peak 3, m/z: 1452.12; peak 4, m/z: 1208.72; peak 5, m/z: 1619.58). All of these peaks had higher expression in the pre-therapy group and were confirmed to be Tubulin beta chain (TUBB), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Complement component 3 (C3), and Complement C4A precursor (C4A) by ELISA validation. Multivariate logistic regression analysis revealed that serum levels of TUBB, ITIH4, C3, and C4A were significant independent risk factors for the development of depression.ConclusionDepression is a prevalent psychiatric condition. Timely detection is challenging, resulting in poor prognoses for patients. Our study on plasma proteomics for depression demonstrated that TUBB, ITIH4, C3, and C4A differentiate between depression patients and healthy controls. The proteins that were identified could potentially function as biomarkers for the diagnosis of depression. Pinpointing these biomarkers could enable early identification of depression, which would advance precise treatment.

Dataset Information

Proteomic Analysis Uncovers Measles Virus Protein C Interaction With p65-iASPP Protein Complex.

Publications

Proteomic Analysis Uncovers Measles Virus Protein C Interaction With p65-iASPP Protein Complex.

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