5 research outputs found

    222— Identifying Regeneration Negative Zebrafish

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    Zebrafish are a useful model organism in studying developmental biology. One topic of interest is their ability to regenerate tissues, including retinal cells. Uncovering genetic pathways for this disease could be applicable to humans, as humans and zebrafish have numerous analogous genes. Scientists use mutants with non-functioning genes to elucidate where genes lie in a pathway. We studied mutants, which are suspected to lack the regenerative abilities of wild type zebrafish; the specific gene is unknown. Our goal was to confirm our family of fish as regenerative mutants. First, they were dark adapted and then placed in intense light for three days. We examined the retinas for regeneration under a fluorescence microscope. If they are regenerating they should be brightly expressing GFP (protein that glows under fluorescent light), but fail to express bright GFP if they are not. The eyes were surgically removed and cryosectioned. From here, the slides will be further examinedunder a confocal microscope in order to see if the antibodies bind to lower numbers of retinal cells in our mutant line compared with normal fish. We then plan on repeating this experiment for the other zebrafish in the same line as these parent zebrafish

    mAb therapy controls CNS-resident lyssavirus infection via a CD4 T cell-dependent mechanism

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    DATA AVAILABILITY : This study includes no data deposited in external repositories.Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre-symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an antilyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11-dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell-dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRc-binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization-independent T cell-mediated effects, even against an established CNS infection by a lethal neurotropic virus.https://www.embopress.org/journal/17574684am2024Medical VirologySDG-03:Good heatlh and well-bein

    mAb therapy controls CNS‐resident lyssavirus infection via a CD4 T cell‐dependent mechanism

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    Abstract Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre‐symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an anti‐lyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11‐dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell‐dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRγ‐binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization‐independent T cell‐mediated effects, even against an established CNS infection by a lethal neurotropic virus

    Genomic Surveillance of Rabies Virus in Georgian Canines

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    Rabies is a fatal zoonosis that is considered a re-emerging infectious disease. Although rabies remains endemic in canines throughout much of the world, vaccination programs have essentially eliminated dog rabies in the Americas and much of Europe. However, despite the goal of eliminating dog rabies in the European Union by 2020, sporadic cases of dog rabies still occur in Eastern Europe, including Georgia. To assess the genetic diversity of the strains recently circulating in Georgia, we sequenced seventy-eight RABV-positive samples from the brain tissues of rabid dogs and jackals using Illumina short-read sequencing of total RNA shotgun libraries. Seventy-seven RABV genomes were successfully assembled and annotated, with seventy-four of them reaching the coding-complete status. Phylogenetic analyses of the nucleoprotein (N) and attachment glycoprotein (G) genes placed all the assembled genomes into the Cosmopolitan clade, consistent with the Georgian origin of the samples. An amino acid alignment of the G glycoprotein ectodomain identified twelve different sequences for this domain among the samples. Only one of the ectodomain groups contained a residue change in an antigenic site, an R264H change in the G5 antigenic site. Three isolates were cultured, and these were found to be efficiently neutralized by the human monoclonal antibody A6. Overall, our data show that recently circulating RABV isolates from Georgian canines are predominantly closely related phylogroup I viruses of the Cosmopolitan clade. Current human rabies vaccines should offer protection against infection by Georgian canine RABVs. The genomes have been deposited in GenBank (accessions: OQ603609-OQ603685)
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