A5005833714- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- Respiratory viral infections research
- Plant Virus Research Studies
- Invertebrate Immune Response Mechanisms
- RNA regulation and disease
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Vectors
- Insect Resistance and Genetics
- RNA Interference and Gene Delivery
- Insect-Plant Interactions and Control
- Clostridium difficile and Clostridium perfringens research
- interferon and immune responses
- SARS-CoV-2 detection and testing
- Parasitic Infections and Diagnostics
- Blood Coagulation and Thrombosis Mechanisms
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Calcium signaling and nucleotide metabolism
- Anesthesia and Neurotoxicity Research
- Cell Image Analysis Techniques
Vanderbilt University Medical Center
2014-2023
Vanderbilt Health
2023
Vanderbilt University
2010-2022
Biology of Infection
2020
National Institute of Allergy and Infectious Diseases
2020
Kaiser Permanente
2020
University of Maryland, Baltimore
2020
Children's Healthcare of Atlanta
2020
Emory University
2020
University of Georgia
2004-2010
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. We conducted phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 55 years age, who received two vaccinations, 28 days apart, with dose 25 μg, 100 or 250 μg. There were 15 participants each group. After...
Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences illness and death from disease 2019 (Covid-19) have been associated age. We conducted a phase 1, dose-escalation, open-label trial messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) healthy adults. The was expanded include 40 adults, who were stratified...
Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, causative agent of COVID-19. Here, we show that ribonucleoside analog β-d-N
Commensal microflora promote the pathogenesis of mucosally acquired viruses.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of novel viral disease COVID-19. With no approved therapies, this pandemic illustrates urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits replication in human lung cells primary airway epithelial cultures (EC50 = 0.01 μM). Weaker activity observed Vero E6 1.65 μM) because their low capacity to metabolize RDV....
A nonpathogenic virus can promote inflammatory immunity to dietary antigens and may be linked the development of celiac disease.
The emergence of coronaviruses (CoVs) into human populations from animal reservoirs has demonstrated their epidemic capability, pandemic potential, and ability to cause severe disease. However, no antivirals have been approved treat these infections. Here, we demonstrate the potent antiviral activity a broad-spectrum ribonucleoside analogue, β- d - N 4 -hydroxycytidine (NHC), against two divergent CoVs. Viral proofreading does not markedly impact sensitivity NHC inhibition, suggesting novel...
Recombination is proposed to be critical for coronavirus (CoV) diversity and emergence of SARS-CoV-2 other zoonotic CoVs. While RNA recombination required during normal CoV replication, the mechanisms determinants are not known. CoVs encode an proofreading exoribonuclease (nsp14-ExoN) that distinct from polymerase responsible high-fidelity synthesis, resistance nucleoside analogues, immune evasion, virulence. Here, we demonstrate CoVs, including SARS-CoV-2, MERS-CoV, model murine hepatitis...
Activators of innate immunity may have the potential to combat a broad range infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent adaptive interferon (IFN, type I II) required receptors Toll-like receptor 5 (TLR5) NOD-like C4 (NLRC4). Flagellin-induced activation TLR5 on dendritic cells elicited production cytokine interleukin-22 (IL-22), which induced protective gene...
The nucleoside analog remdesivir (RDV) is a Food and Drug Administration-approved antiviral for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, it critical to understand factors that promote or prevent RDV resistance. We passaged SARS-CoV-2 in the presence increasing concentrations GS-441524, parent RDV. After 13 passages, we isolated three viral lineages with phenotypic resistance as defined by increases half-maximal effective concentration from...
Nucleotide metabolic pathways provide numerous successful targets for antiparasitic chemotherapy, but the human pathogen Cryptosporidium parvum thus far has proved extraordinarily refractory to classical treatments. Given importance of this protist as an opportunistic afflicting immunosuppressed individuals, effective treatments are urgently needed. The genome sequence C. is approaching completion, and we have used resource critically assess nucleotide biosynthesis a target in . Genomic...
ABSTRACT In mouse embryonic fibroblasts (MEFs), the bovine rotavirus (UK strain) but not simian rhesus (RRV) robustly triggers beta interferon (IFN-β) secretion, resulting in an IFN-dependent restriction of replication. We now find that both strains trigger antiviral transcriptional responses early during infection and IFN-β secretion are completely abrogated MAVS/IPS-1 −/− MEFs. Replication UK virus could be rescued MEFs, synthesis viral RNA significantly increased infection. induced...
Infection of cultured insect cells with Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV) resulted in the generation mutants major genomic deletions. Some lacked ability to infect S. larvae per os. The gene(s) responsible for this phenotype SeMNPV was mapped within a contiguous sequence encoding ORFs 29-35. In paper we have shown that 15-35 (including genes cathepsin, chitinase, GP37, PTPT-2, EGT, PKIP-1 and ARIF-1) are not essential virus replication cell culture or by vivo...
ABSTRACT Coronaviruses (CoVs) encode nonstructural proteins 1–16 (nsps 1–16) which form replicase complexes that mediate viral RNA synthesis. Remdesivir (RDV) is an adenosine nucleoside analog antiviral inhibits CoV RDV resistance mutations have been reported only in the protein 12 RNA-dependent polymerase (nsp12-RdRp). We here show a substitution mutation nsp13-helicase (nsp13-HEL A335V) of betacoronavirus murine hepatitis virus (MHV) was selected during passage with parent compound confers...
Viruses in the family Polydnaviridae are symbiotically associated with parasitoid wasps. Wasps inject polydnaviruses (PDVs) when laying an egg into their insect host, and expression of viral gene products causes several physiological alterations, including immunosuppression, that allow wasp's progeny to develop. As other PDVs, most Microplitis demolitor bracovirus (MdBV) genes related variants form families. The largest MdBV includes 13 members encode predicted proteins protein tyrosine...
ABSTRACT Several viruses induce intestinal epithelial cell death during enteric infection. However, it is unclear whether proapoptotic capacity promotes or inhibits replication in this tissue. We infected mice with two reovirus strains that infect the intestine but differ to alter immunological tolerance new food antigen. Infection strain T1L, which induces an inflammatory immune response fed antigen, prolonged intestine, whereas T3D-RV, does not response, rapidly cleared from intestine....
SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of novel pandemic viral disease COVID-19. With no approved therapies, this illustrates urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug an adenosine analog, potently inhibits replication human lung cells primary airway epithelial cultures (EC 50 = 0.01 μM). Weaker...
Abstract Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2. Herein, we show that ribonucleoside analog β-D-N 4 -hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well increased potency a coronavirus bearing resistance mutations to another nucleoside inhibitor. In mice infected with...
The unprecedented scale of the COVID-19 pandemic and rapid evolution SARS-CoV-2 variants underscore need for broadly active inhibitors with a high barrier to resistance. coronavirus main protease (M
SUMMARY Insect pathogens and parasites often affect the growth development of their hosts, but understanding these processes is fragmentary. Among most species-rich important mortality agents insects are parasitoid wasps that carry symbiotic polydnaviruses (PDVs). Like many PDV-carrying wasps, Microplitis demolitor inhibits pupation its lepidopteran host, Pseudoplusia includens, by causing host hemolymph juvenile hormone (JH) titers to remain elevated preventing ecdysteroid from rising. Here...
Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-κB-driven transcription of proapoptotic cellular genes is required for effector phase apoptotic response. Although extrinsic death-receptor signaling pathways intrinsic involving mitochondrial injury are implicated reovirus-induced apoptosis, mechanisms by which either these activated their relationship NF-κB following reovirus unknown. The Bcl-2 family member, Bid, proteolytic...