A5054415798- interferon and immune responses
- Poxvirus research and outbreaks
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Microbial Natural Products and Biosynthesis
- Bacillus and Francisella bacterial research
- Influenza Virus Research Studies
- RNA regulation and disease
- HIV Research and Treatment
- Immune Cell Function and Interaction
- DNA Repair Mechanisms
- Cancer Research and Treatments
- RNA Research and Splicing
- Galectins and Cancer Biology
- Animal Virus Infections Studies
- Protease and Inhibitor Mechanisms
- Immune cells in cancer
- Cancer Cells and Metastasis
- Genomics and Chromatin Dynamics
- Cytokine Signaling Pathways and Interactions
- vaccines and immunoinformatics approaches
- Extracellular vesicles in disease
- Sperm and Testicular Function
- CRISPR and Genetic Engineering
Universidad Autónoma de Madrid
2016-2025
Icahn School of Medicine at Mount Sinai
2022-2025
Hospital Universitario La Paz
2025
Secretaría de Investigación, Innovación y Educación Superior
2023
Centro de Biología Molecular Severo Ochoa
2001-2021
Universidad de León
2006-2014
Consejo Superior de Investigaciones Científicas
2001-2013
Instituto de Biotecnología de León
2007-2012
Centro Nacional de Biotecnología
2002-2011
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2009
Abstract Exosomes are vesicles secreted to the extracellular environment through fusion with plasma membrane of specific endosomes called multivesicular bodies (MVB) and mediate cell-to-cell communication in many biological processes. Posttranslational modifications involved sorting proteins into exosomes. Here we identify ISGylation as a ubiquitin-like modification that controls exosome release. induction decreases MVB numbers impairs secretion. Using ISG15-knockout mice expressing...
The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or IIa MPXV, possibly genomic changes MPXV. Key could occur the genome's low-complexity regions (LCRs), which are challenging sequence and often dismissed as uninformative. Here, using combination highly sensitive techniques, we determine high-quality MPXV genome representative current with LCRs...
Cancer stem cells (CSC) are thought to play a major role in the development and metastatic progression of pancreatic ductal adenocarcinoma (PDAC), one deadliest solid tumors. Likewise, tumor microenvironment contributes critical support this setting, including from stromal tumor-associated macrophages (TAM) that contribute structural paracrine-mediated supports, respectively. Here, we show TAMs secrete IFN-stimulated factor ISG15, which enhances CSC phenotypes PDAC vitro vivo. ISG15 was...
Protein modification by the ubiquitin-like protein ISG15 is an interferon (IFN) effector system, which plays a major role in antiviral defense. counteracted isopeptidase USP18, negative regulator of IFN signaling, was also shown to exert its regulatory function isopeptidase-independent manner. To dissect enzymatic and nonenzymatic functions USP18 vivo, we generated knock-in mice (USP18(C61A/C61A)) expressing enzymatically inactive USP18. USP18(C61A/C61A) displayed increased levels...
Monkeypox virus (MPXV) is a zoonotic orthopoxvirus within the Poxviridae family. MPXV endemic to Central and West Africa. However, world currently witnessing an international outbreak with no clear epidemiological links travel or animal exposure ever-increasing numbers of reported cases worldwide. Here, we evaluated validated new, sensitive, specific real-time PCR-assay for diagnosis in humans compare performance this novel assay against Food & Drug Administration-cleared pan-Orthopox RT-PCR...
The Interferon Stimulated Gene 15 (ISG15), a unique Ubiquitin-like (Ubl) modifier exclusive to vertebrates, plays crucial role in the immune system. Primarily induced by interferon (IFN) type I, ISG15 functions through diverse mechanisms: (i) covalent protein modification (ISGylation); (ii) non-covalent intracellular action; and (iii) exerting extracellular cytokine activity. These various roles highlight its versatility influencing numerous cellular pathways, encompassing DNA damage...
The double-stranded RNA (dsRNA)-dependent protein kinase PKR activates NF-κB via the IκB (IKK) complex, but little is known about additional molecules that may be involved in this pathway. Analysis of sequence enabled us to identify two putative TRAF-interacting motifs. viability such an interaction was further suggested by computer modeling. Here, we present evidence colocalization and physical between TRAF family proteins vivo, as shown immunoprecipitation confocal microscopy experiments....
The ubiquitin-like modifier ISG15 is one of the most predominant proteins induced by type I interferons (IFN). In this study, murine embryo fibroblast (MEFs) and mice lacking gene were used to demonstrate a novel role as host defense molecule against vaccinia virus (VACV) infection. MEFs, growth replication competent Western Reserve (WR) VACV strain was affected absence ISG15, but in addition, E3 protein (VVΔE3L) that unable grow ISG15+/+ cells replicated ISG15-deficient cells. Inhibiting...
The interferon (IFN)-stimulated gene 15 (ISG15) encodes one of the most abundant proteins induced by interferon, and its expression is associated with antiviral immunity. To identify protein components implicated in IFN ISG15 signaling, we compared proteomes ISG15-/- ISG15+/+ bone marrow derived macrophages (BMDM) after vaccinia virus (VACV) infection. results this analysis revealed that mitochondrial dysfunction oxidative phosphorylation (OXPHOS) were pathways altered BMDM treated IFN....
ABSTRACT Vaccinia virus (VV) is a cytocidal that causes major changes in host cell machinery shortly after infecting cells. To define the consequences of infection on gene expression, we used microarrays approximately 15,000 human cDNAs to examine expression levels mRNAs isolated at 2, 6, and 16 h postinfection from cultures infected HeLa The majority profiling during VV corresponded downregulation genes postinfection. Differentially expressed were clustered into seven groups identify common...
ABSTRACT Although recombinants based on the attenuated poxvirus vectors MVA and NYVAC are currently in clinical trials, nature of genes triggered by these antigen-presenting cells is poorly characterized. Using microarray technology various analysis conditions, we compared specific changes gene expression profiling following infection immature human monocyte-derived dendritic (MDDC). Microarray was performed at 6 h postinfection, since viruses induced extensive cytopathic effects, rRNA...
Sequencing of the DNA region on left fringe pimaricin gene cluster revealed presence a 579 bp gene, pimM, whose deduced product (192 aa) was found to have amino acid sequence homology with bacterial regulatory proteins. Database comparisons that PimM combines an N-terminal PAS domain C-terminal helix–turn–helix (HTH) motif LuxR type. Gene replacement pimM from Streptomyces natalensis chromosome mutant version lacking HTH DNA-binding resulted in complete loss production, suggesting is...
Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces reversible post-translational modification (ISGylation) and can also be secreted as free form. ISG15 plays an essential role host-defence response to microbial infection; however, its contribution vascular damage associated with hypertension is unknown.Bioinformatics identified mediator of hypertension-associated damage. expression positively correlated systolic diastolic blood pressure carotid intima-media...
Monkeypox (MPOX) is a zoonotic disease endemic to regions of Central/Western Africa. The geographic endemicity MPV has expanded, broadening the human-monkeypox virus interface and its potential for spillover. Since May 2022, large multi-country outbreak with no proven links countries originated in Europe rapidly expanded around globe, setting off genomic surveillance efforts. Here, we conducted analysis 23 MPV-infected patients from New York City during early outbreak, assessing phylogenetic...
ABSTRACT The potential use of the modified vaccinia virus Ankara (MVA) strain as a live recombinant vector to deliver antigens and elicit protective immune responses against infectious diseases demands comprehensive understanding effect MVA infection on human host gene expression. We used microarrays containing more than 15,000 cDNAs identify expression changes in HeLa cell cultures at 2, 6, 16 h postinfection. Clustering 410 differentially regulated genes identified 11 discrete clusters...
The cortical actin cytoskeleton beneath the plasma membrane represents a physical barrier that vaccinia virus has to overcome during its exit from an infected cell. Previous observations using overexpression and pharmacological approaches suggest enhances release by modulating inhibiting RhoA signalling viral protein F11. We have now examined role of F11 ability interact with inhibit downstream in spread infection both vitro vivo. Live cell imaging over 48 hours reveals loss or bind...
There is a need to develop universal vaccine against influenza virus infection avoid developing new formulations of seasonal each year. Many the strategies for target strain-conserved proteins, such as matrix, polymerase, and nucleoproteins, rather than surface hemagglutinin neuraminidase proteins. In addition, non-disease-causing viral vectors are popular choice delivery system antigens. As proof-of-concept, we have designed novel immunogen based on NP backbone containing human T cell...
Abstract PrimPol is a human primase/polymerase specialized in re-starting stalled forks by repriming beyond lesions such as pyrimidine dimers, and replication-perturbing structures including G-quadruplexes R-loops. Unlike most conventional primases, proficiently discriminates against ribonucleotides ( NTPs ), being able to start synthesis using deoxynucleotides (dNTPs), yet the structural basis physiological implications for this discrimination are not understood. In silico analyses based on...
ABSTRACT Vaccines that elicit systemic and mucosal immune responses should be the choice to control human immunodeficiency virus (HIV) infections. We have previously shown prime-boost immunizations with influenza Env vaccinia (VV) WR recombinants induced an enhanced CD8 + T-cell response against HIV-1 antigen. In this report, we analyzed in BALB/c mice after priming ability of two VV expressing B (VV highly attenuated modified Ankara [MVA] Env) boost cellular spleen lymph nodes draining...
ABSTRACT Live recombinants based on attenuated modified vaccinia virus Ankara (MVA) are potential vaccine candidates against a broad spectrum of diseases and tumors. To better understand the efficacy MVA as human vaccine, we analyzed by confocal electron microscopy approaches MVA-induced morphological changes morphogenetic stages during infection HeLa cells in comparison to other strains (VV): wild-type Western Reserve (WR), Ankara, New York City Board Health (NYCBH) strains. Confocal...