- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Advanced Thermodynamic Systems and Engines
- Escherichia coli research studies
- Cancer Cells and Metastasis
- Clinical Nutrition and Gastroenterology
- 3D Printing in Biomedical Research
- Respiratory viral infections research
- Hepatitis Viruses Studies and Epidemiology
- Digestive system and related health
- Clostridium difficile and Clostridium perfringens research
- Infant Nutrition and Health
- Tissue Engineering and Regenerative Medicine
- Microscopic Colitis
- Biofuel production and bioconversion
- Parvovirus B19 Infection Studies
- Heat shock proteins research
- Probiotics and Fermented Foods
- Food Quality and Safety Studies
- Edible Oils Quality and Analysis
- Plant Virus Research Studies
- Essential Oils and Antimicrobial Activity
- Viral Infections and Vectors
Baylor College of Medicine
2015-2024
Universidade de Santiago de Compostela
2022
Centro de Investigaciones Biológicas Margarita Salas
2022
Baylor University
2020
Centers for Disease Control and Prevention
2018
Oak Ridge Associated Universities
2018
Synergy America (United States)
2018
Montana State University
2002-2011
Sidi Mohamed Ben Abdellah University
2000-2001
The major barrier to research and development of effective interventions for human noroviruses (HuNoVs) has been the lack a robust reproducible in vitro cultivation system. HuNoVs are leading cause gastroenteritis worldwide. We report successful multiple HuNoV strains enterocytes stem cell–derived, nontransformed intestinal enteroid monolayer cultures. Bile, critical factor milieu, is required strain-dependent replication. Lack appropriate histoblood group antigen expression cells restricts...
Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate cellular diversity and complex functions human physiology disease pathology. enteroid (HIE) cultures contain multiple epithelial types comprise epithelium (enterocytes goblet, enteroendocrine, Paneth cells) are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE as for pathogenic infections small intestine examining...
Abstract Human noroviruses are a leading cause of epidemic and endemic acute gastroenteritis worldwide foodborne illness in the United States. Recently, human intestinal enteroids (HIEs) derived from small tissue have been shown to support norovirus replication. We implemented HIE system our laboratory tested effect chlorine alcohols on infectivity. Successful replication was observed for 6 GII genotypes dependent viral load genotype inoculum. GII.4 viruses had higher levels than other...
Human noroviruses (HuNoVs) are the leading cause of epidemic and sporadic acute gastroenteritis worldwide. We previously demonstrated human intestinal stem cell-derived enteroids (HIEs) support cultivation several HuNoV strains. However, HIEs did not virus replication from every HuNoV-positive stool sample, which led us to test optimize new medium conditions, identify characteristics samples that allow replication, evaluate consistency over time. Optimization our HIE-HuNoV culture system has...
Mechanisms by which viruses counter innate host defense responses generally involve inhibition of one or more components the interferon (IFN) system. Multiple steps in induction and amplification IFN signaling are targeted for viral proteins, many antagonists have direct indirect effects on activation latent cytoplasmic transcription factors. Rotavirus nonstructural protein NSP1 blocks type I IFNα/β inducing proteasome-dependent degradation IFN-regulatory factors 3 (IRF3), IRF5, IRF7. In...
Human noroviruses (HuNoVs) can often cause chronic infections in solid organ and haematopoietic stem cell transplant (HSCT) patients. Based on histopathological changes observed during HuNoV infections, the intestine is presumed site of virus replication patients; however, types infected by HuNoVs remain unknown. The objective this study was to characterize infection determine that may be permissive for We analysed biopsies from HuNoV-infected non-infected (control) patients assess...
Significance Many viral pathogens replicate in the human small intestine where they must invade epithelial barrier that has evolved to protect host against microbial assaults. Using a norovirus strain requires bile stem cell-derived intestinal enteroid cultures, we found conjugated hydrophobic acids and ceramide are critical allow virus entry subsequent replication jejunal enteroids. Glycochenodeoxycholic acid treatment of enteroids below micellar concentration leads multiple cellular...
Several studies have demonstrated that secretor status is associated with susceptibility to human norovirus (HuNoV) infection; however, previous reports found FUT2 expression not sufficient allow infection HuNoV in a variety of continuous laboratory cell lines. Which cellular factor(s) regulates remains unknown. We used genetic manipulation HIE cultures show determined by gene necessary and support replication based on analyses isogenic lines lack or express FUT2. Fucosylation HBGAs critical...
Human noroviruses (HuNoVs) are the leading cause of viral gastroenteritis worldwide; yet currently, no vaccines or FDA-approved antiviral drugs available to counter these pathogens. To understand HuNoV biology and epithelial response infection, we performed transcriptomic analyses, RT-qPCR, CRISPR-Cas9 modification human intestinal enteroid (HIE) cultures, functional studies with two virus strains (a pandemic GII.4 a bile acid-dependent GII.3 strain). We identified predominant type III...
Abstract Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these exploit for cell entry and internalization unknown. Here, using nontransformed jejunal enteroids (HIEs) recapitulate the physiology gastrointestinal tract, we show infectious virions virus-like particles endocytosed a unique combination endosomal acidification-dependent clathrin-independent carriers...
Nisin Z and thymol were tested, alone in combination, for antibacterial activity against Listeria monocytogenes ATCC 7644 Bacillus subtilis 33712. The effect of nisin Z, produced by Lactococcus lactis KE3 isolated from the traditional Moroccan fermented milk, was greatly potentiated sub-inhibitory concentrations both bacterial strains. Our data showed that concentration required effective control food-borne pathogenic bacteria could be considerably lowered use combination. low lead to a less...
Murine norovirus (MNoV) is an important model of human (HNoV) and mucosal virus infection more broadly. Viral receptor utilization a major determinant cell tropism, host range, pathogenesis. The bona fide for HNoV unknown. Recently, we identified CD300lf as proteinaceous MNoV. Interestingly, its paralogue CD300ld was also sufficient MNoV in vitro. Here explored whether the sole physiologic vivo can use CD300 ortholog entry receptor. We report that both are by diverse strains further...
Abstract The rational development of norovirus vaccine candidates requires a deep understanding the antigenic diversity and mechanisms neutralization virus. Here, we isolate characterize panel broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs IgGs reactive with (HuNoV) genogroup I or II (GI GII). We note three binding patterns identify antibodies (mAbs) that neutralize at least one GI GII HuNoV strain when using histo-blood group antigen (HBGA) blocking assay. HBGA assay...
Little data on the persistence of human norovirus infectivity are available to predict its transmissibility. Using intestinal enteroids, we demonstrate that 2 strains can remain infectious for several weeks in seawater. Such experiments improve understanding factors associated with survival coastal waters and shellfish.
Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants new antigenic profiles altered specificity for histo-blood group antigens (HBGA), the determinants cell attachment susceptibility, hampering development immunotherapeutics. Here, we show that llama-derived nanobody...
Human sapoviruses (HuSaVs), like human noroviruses (HuNoV), belong to the Caliciviridae family and cause acute gastroenteritis in humans. Since their discovery 1976, numerous attempts grow HuSaVs vitro were unsuccessful until 2020, when these viruses reported replicate a duodenal cancer cell-derived line. Physiological cellular models allowing viral replication are essential investigate HuSaV biology mechanisms such as genetic susceptibility, restriction factors, immune responses infection....
ABSTRACT Human noroviruses (HuNoVs) are a significant cause of epidemic and sporadic acute gastroenteritis worldwide. The lack reproducible culture system hindered the study HuNoV replication pathogenesis for almost half-century. This barrier was overcome with our successful cultivation multiple strains in human intestinal enteroids (HIEs), which has significantly advanced research. We optimized media conditions generated genetically modified HIE cultures to enhance HIEs. Building upon these...
In vitro models, such as primary cells and continuous cell lines routinely used for evaluating drug candidates, have limitations in their translational relevance to human diseases. Organotypic cultures are increasingly being assess therapeutics various cancers infectious Monitoring cytotoxicity is crucial development, several commercially available kits assessment offer distinct advantages limitations. Given the complexity of organoid cultures, including donor-driven variability, we...
Norwalk virus (NV), a reference strain of human calicivirus in the Norovirus genus family Caliciviridae, contains positive-strand RNA genome with three open reading frames. ORF1 encodes 1,789-amino-acid polyprotein that is processed into nonstructural proteins include an NTPase, VPg, protease, and RNA-dependent polymerase. The N-terminal protein p48 shows no significant sequence similarity to viral or cellular proteins, its function replication cycle not known. lack any public databases...
During olive oil production, large quantities of mill wastewater (OMW) are produced. This material, containing a high level phenolic compounds, poses serious environmental problem in almost all Mediterranean countries. Candida tropicalis YMEC14 was used as an extremophile strain to design aerobic biotreatment process detoxify OMW and reduce its polluting organic load. The enhanced by directing yeast metabolism towards biodegradation pathways using hexadecane co-metabolite immobilizing cells...
Interferon regulatory factor 3 (IRF3) is a key transcription involved in the induction of interferon (IFN) response to viral infection. Rotavirus non-structural protein NSP1 binds and targets IRF3 for proteasome degradation early post-infection. Mutational analysis cysteine histidine residues within conserved N-terminal zinc-binding domain bovine rotavirus strain B641 abolished transfected cells. Thus, integrity important IRF3. In contrast B641, was stable cells infected with porcine OSU...