A5078588001- Viral Infections and Outbreaks Research
- Virus-based gene therapy research
- Viral Infections and Vectors
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Virology and Viral Diseases
- interferon and immune responses
- Hepatitis B Virus Studies
- Plant Virus Research Studies
- Poxvirus research and outbreaks
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Rabies epidemiology and control
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- Disaster Response and Management
- Viral Infections and Immunology Research
- Long-Term Effects of COVID-19
- Microbial infections and disease research
- Cytomegalovirus and herpesvirus research
- Vagus Nerve Stimulation Research
- CAR-T cell therapy research
- Biochemical and Molecular Research
- CRISPR and Genetic Engineering
Scripps Research Institute
2011-2025
Scripps Institution of Oceanography
2020-2023
Scripps (United States)
2022-2023
The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I virus (MPXV) strain than the II associated with 2022 global mpox outbreak, which led WHO declare this public health emergency of international concern. FDA-approved small molecule antiviral tecovirimat (TPOXX) recommended treat cases severe symptoms, but limited efficacy TPOXX emergence resistant MPXV variants challenged medical...
We have previously demonstrated that Borna disease virus (BDV) has a negative nonsegmented single-stranded (NNS) RNA genome replicates in the nucleus of infected cells. Here we report for first time cloning and complete sequence BDV genome. Our results revealed genomic organization similar to other members Mononegavirales order. identified five main open reading frames (ORFs). The largest ORF, V, is located closest 5' end and, on basis strong homology with NNS-RNA polymerases, member...
We have documented that the nucleoprotein (NP) of prototypic arenavirus lymphocytic choriomeningitis virus is an antagonist type I interferon response. In this study we tested ability NPs encoded by representative species from both Old World and New antigenic groups to inhibit production interferon. found that, with exception Tacaribe (TCRV), all inhibited activation beta regulatory factor 3 (IRF-3)-dependent promoters, as well nuclear translocation IRF-3. Consistent observation,...
Borna disease virus (BDV) causes neurological in a wide range of animal species, providing an important model for studies persistent viral infection the central nervous system. In addition, detection antibodies that react with BDV antigen serum from psychiatric patients suggests role BDV, or related viruses, human mental disorders, further reason study this poorly characterized neurotropic virus. We present evidence has nonsegmented negative single-strand RNA genome property replication and...
In several vertebrate species, Borna disease virus (BDV), the prototype of a new group animal viruses, causes central nervous system accompanied by diverse behavioral abnormalities. Seroepidemiological data indicate that BDV may contribute to pathophysiology certain human mental disorders. This hypothesis is further supported detection both antigens and RNA in peripheral blood mononuclear cells (PBMCs) patients with psychiatric disorders isolation from such PBMCs. Here we describe...
Lymphocytic choriomeningitis virus (LCVM) nucleoprotein (NP) counteracts the host type I interferon (IFN) response by inhibiting activation of IFN regulatory factor 3 (IRF3). In this study, we have mapped regions and specific amino acid residues within NP involved in its anti-IFN activity. We identified a region spanning 382 to 386 as playing critical role IFN-counteracting activity NP. Alanine substitutions at several positions resulted mutants that lacked but retained their functions RNA...
We have investigated the entry pathway of Borna disease virus (BDV). Virus was assessed by detecting early viral replication and transcription. Lysosomotropic agents (ammonium chloride, chloroquine, amantadine), as well energy depletion, prevented BDV infection, indicating that enters host cells endocytosis requires an acidic intracellular compartment to allow membrane fusion initiate infection. Consistent with this hypothesis, we observed BDV-infected form extensive syncytia upon low-pH...
Significance Zaire ebolavirus (EBOV) is a viral pathogen of significant global health concern best exemplified by more than 28,000 human infections during the recent West African epidemic. Examining immunity in EBOV disease survivors has been historically difficult due to occurrence only small outbreaks remote regions central Africa. Consequently, little data exist describing EBOV-specific T cell responses infection. We examined virus-specific CD8 + 32 Sierra Leonean 2013–2016 cells against...
Borna disease virus (BDV) is a nonsegmented negative-stranded (NNS) RNA virus, prototype of new taxon in the Mononegavirales order. BDV causes neurologic manifested by behavioral abnormalities several animal species, and evidence suggests that it may be human pathogen. To improve our knowledge about biology this novel we have identified characterized product open reading frame IV (BVp56). Based on sequence features, BVp56 encodes surface glycoprotein. Glycoproteins play essential roles NNS...
ABSTRACT Several arenaviruses cause hemorrhagic fever disease in humans and represent important public health problems the regions where these viruses are endemic. In addition, evidence indicates that worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is an neglected human pathogen. There no licensed vaccines current antiarenavirus therapy limited to use of ribavirin only partially effective. Therefore, there unmet need for novel antiarenaviral...
Lassa virus (LASV), a mammarenavirus, infects an estimated 100,000⁻300,000 individuals yearly in western Africa and frequently causes lethal disease. Currently, no LASV-specific antivirals or vaccines are commercially available for prevention treatment of fever, the disease caused by LASV. The development medical countermeasure screening platforms is crucial step to yield licensable products. Using reverse genetics, we generated recombinant wild-type LASV (rLASV-WT) modified version thereof...
ABSTRACT Many viruses, including mammarenaviruses, have evolved mechanisms to counteract different components of the host cell innate immunity, which is required facilitate robust virus multiplication. The double-stranded RNA (dsRNA) sensor protein kinase receptor (PKR) pathway plays a critical role in anti-viral response. Whether PKR can restrict multiplication Old World mammarenavirus lymphocytic choriomeningitis (LCMV) and by LCMV may functions not yet been investigated. Here we present...
Borna disease virus (BDV) is an enveloped virus. Its non-segmented, negative-stranded RNA genome has the coding capability for six main polypeptides and organization characteristic of members order Mononegavirales. However, based on its unique genetics biological features, BDV considered to be prototypic member a new family, Bornaviridae. Here, establishment reverse system described. Intracellular synthesis analogue or minigenome (MG) from plasmid was driven by polymerase I. Co-transfection...
ABSTRACT Hemorrhagic fever arenaviruses (HFA) pose important public health problems in regions where they are endemic. Thus, Lassa virus (LASV) infects several hundred thousand individuals yearly West Africa, causing a large number of cases associated with high morbidity and mortality. Concerns about human-pathogenic exacerbated because the lack FDA-licensed arenavirus vaccines current antiarenaviral therapy is limited to an off-label use ribavirin that only partially effective. The Mopeia...
Neurological complications are common in patients with COVID-19. While SARS-CoV-2, the causal pathogen of COVID-19, has been detected some patient brains, its ability to infect brain cells and impact their function not well understood, experimental models using human urgently needed. Here we investigated susceptibility induced pluripotent stem cell (hiPSC)-derived monolayer region-specific organoids SARS-CoV-2 infection. We found modest numbers infected neurons astrocytes, but greater...
Lassa fever (LF), a viral hemorrhagic disease with case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed prevent treat LF, hence the significance of developing therapeutics against mammarenavirus virus (LASV), causative agent LF. We used in silico docking approaches investigate binding affinities 2015 existing drugs LASV proteins known play critical roles formation and...
Lassa virus infects hundreds of thousands people each year across rural West Africa, resulting in a high number cases fever (LF), febrile disease associated with morbidity and significant mortality. The lack approved treatments or interventions underscores the need for an effective vaccine. At least four viral lineages circulate defined regions throughout Africa substantial interlineage nucleotide amino acid diversity. An vaccine should be designed to elicit specific humoral cell mediated...
The eukaryotic chaperonin containing tailless complex polypeptide 1 ring (CCT, also known as TCP-1 Ring Complex, TRiC/CCT) participates in the folding of 5% to 10% cellular proteome and has been involved life cycle several viruses, including dengue, Zika, influenza but mechanisms by which TRiC/CCT contributes virus multiplication remain poorly understood. Here, we document that nucleoprotein (NP) mammarenavirus lymphocytic choriomeningitis (LCMV) is a substrate human complex, pharmacological...