Yager, Eric Publications

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    Modulation of Zika virus replication via glycosphingolipids.
    (Virology, 7/1/2022) Konan, Kouacou V; Ogbamikael, Simon Alem; Yager, Eric; Yamaji, Toshiyuki; Cerone, Jennifer; Monaco-Brown, Meredith; Barroso, Margarida; Hanada, Kentaro
    The enveloped positive-sense RNA viruses including Zika virus (ZIKV) need host lipids to successfully replicate. The nature of the lipids and the replication step(s) where lipids are utilized often vary amongst viruses. In this study, we demonstrate that ZIKV particle envelope is significantly enriched in distinct sphingolipid species. To determine the role of sphingolipids in ZIKV replication, we leveraged a panel of sphingolipid-deficient cell lines. Notably, knockout of glucosylceramide and lactosylceramide synthase encoding genes (GCS; B4G5) resulted in a marked decrease in ZIKV titers. GCS or pharmacological inhibition of GCS also led to a significant decrease in ZIKV genome replication. Further analysis indicated that GCS reduced intracellular virus titers but had minimal impact on ZIKV binding. Restoration of B4G5 expression in B4G5 cells or supplementing PDMP-treated cells with glucosylceramide led to a significant rescue of ZIKV replication. Altogether, our findings suggest that ZIKV needs glycosphingolipids to facilitate virus replication.
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    Antibody-dependent enhancement and COVID-19: Moving toward acquittal.
    (Clinical Immunology, 2020-08) Yager, Eric J
    * Immunoglobulins represent an effective therapeutic option for the treatment of COVID-19. * Experimental findings of ADE with related coronaviruses provoked theoretical concerns of enhancing antibodies with COVID-19. * Emerging experimental and clinical data alleviate concerns and indorse the safety of antibody-based therapies for COVID-19.
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    Sphingolipids as Potential Therapeutic Targets against Enveloped Human RNA Viruses.
    (Viruses, 10/1/2019) Yager, Eric J; Konan, Kouacou V
    Several notable human diseases are caused by enveloped RNA viruses: influenza, AIDS, hepatitis C, dengue hemorrhagic fever, microcephaly, and Guillain-Barré Syndrome. Being enveloped, the life cycle of this group of viruses is critically dependent on host lipid biosynthesis. Viral binding and entry involve interactions between viral envelope glycoproteins and cellular receptors localized to lipid-rich regions of the plasma membrane. Subsequent infection by these viruses leads to reorganization of cellular membranes and lipid metabolism to support the production of new viral particles. Recent work has focused on defining the involvement of specific lipid classes in the entry, genome replication assembly, and viral particle formation of these viruses in hopes of identifying potential therapeutic targets for the treatment or prevention of disease. In this review, we will highlight the role of host sphingolipids in the lifecycle of several medically important enveloped RNA viruses.
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    Optimizing particle-mediated epidermal delivery of an influenza DNA vaccine in ferrets.
    (Methods in Molecular Biology, 2013) Yager, Eric J; Stagnar, Cristy; Gopalakrishnan, Ragisha; Fuller, James T; Fuller, Deborah H
    Particle-mediated DNA delivery technologies ("gene guns") have been shown in both animal and clinical studies to be an effective means of increasing the immunogenicity and protective efficacy of DNA vaccines. The primary goal in optimizing particle-mediated epidermal delivery (PMED) vaccination in different animal models is to achieve delivery of DNA-coated gold beads into the viable epidermis. Two key para-meters that influence this outcome include the delivery pressure, which controls the penetrative force of the beads into the skin, and the anatomical site of DNA delivery. Although the ferret has been extensively used as an experimental model for influenza infection in humans, very few studies have investigated the capacity for PMED DNA vaccination to induce protective immune responses in ferrets. Here we describe methods to optimize DNA vaccine delivery using the PowderJect XR1 gene delivery in ferrets. We first assess the effects of firing pressure on both the delivery of DNA-coated gold beads into the desired epidermal layer and the degree of DNA vaccine reporter gene expression at the target site. Second, we evaluate the impact of vaccination site (skin or tongue) on DNA vaccine immunogenicity by measuring serum antibody responses to the model antigens influenza virus hemagglutinin and hepatitis B core antigen. Results from these studies support the use of the PowderJect XR1 device in ferrets for the study of prophylactic and therapeutic DNA vaccines against clinically important diseases such as influenza virus infection.