Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies

Abstract Declines in managed honey bee populations are multifactorial but closely associated with reduced virus immunocompetence and thus, mechanisms to enhance immune function are likely to reduce viral infection rates and increase colony viability. However, gaps in knowledge regarding physiologica...

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Main Authors: Christopher J. Fellows, Michael Simone-Finstrom, Troy D. Anderson, Daniel R. Swale
Format: Article
Language:English
Published: BMC 2023-06-01
Series:Virology Journal
Subjects:
Online Access:https://doi.org/10.1186/s12985-023-02104-0
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author Christopher J. Fellows
Michael Simone-Finstrom
Troy D. Anderson
Daniel R. Swale
author_facet Christopher J. Fellows
Michael Simone-Finstrom
Troy D. Anderson
Daniel R. Swale
author_sort Christopher J. Fellows
collection DOAJ
description Abstract Declines in managed honey bee populations are multifactorial but closely associated with reduced virus immunocompetence and thus, mechanisms to enhance immune function are likely to reduce viral infection rates and increase colony viability. However, gaps in knowledge regarding physiological mechanisms or ‘druggable’ target sites to enhance bee immunocompetence has prevented therapeutics development to reduce virus infection. Our data bridge this knowledge gap by identifying ATP-sensitive inward rectifier potassium (KATP) channels as a pharmacologically tractable target for reducing virus-mediated mortality and viral replication in bees, as well as increasing an aspect of colony-level immunity. Bees infected with Israeli acute paralysis virus and provided KATP channel activators had similar mortality rates as uninfected bees. Furthermore, we show that generation of reactive oxygen species (ROS) and regulation of ROS concentrations through pharmacological activation of KATP channels can stimulate antiviral responses, highlighting a functional framework for physiological regulation of the bee immune system. Next, we tested the influence of pharmacological activation of KATP channels on infection of 6 viruses at the colony level in the field. Data strongly support that KATP channels are a field-relevant target site as colonies treated with pinacidil, a KATP channel activator, had reduced titers of seven bee-relevant viruses by up to 75-fold and reduced them to levels comparable to non-inoculated colonies. Together, these data indicate a functional linkage between KATP channels, ROS, and antiviral defense mechanisms in bees and define a toxicologically relevant pathway that can be used for novel therapeutics development to enhance bee health and colony sustainability in the field.
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spelling doaj.art-7fcf5266e99d4e8db654b95f4855576f2023-06-25T11:09:00ZengBMCVirology Journal1743-422X2023-06-0120111710.1186/s12985-023-02104-0Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee coloniesChristopher J. Fellows0Michael Simone-Finstrom1Troy D. Anderson2Daniel R. Swale3Department of Entomology, Louisiana State University AgCenterUSDA-ARS Honey Bee Breeding, Genetics, and Physiology LaboratoryDepartment of Entomology, University of NebraskaDepartment of Entomology, Louisiana State University AgCenterAbstract Declines in managed honey bee populations are multifactorial but closely associated with reduced virus immunocompetence and thus, mechanisms to enhance immune function are likely to reduce viral infection rates and increase colony viability. However, gaps in knowledge regarding physiological mechanisms or ‘druggable’ target sites to enhance bee immunocompetence has prevented therapeutics development to reduce virus infection. Our data bridge this knowledge gap by identifying ATP-sensitive inward rectifier potassium (KATP) channels as a pharmacologically tractable target for reducing virus-mediated mortality and viral replication in bees, as well as increasing an aspect of colony-level immunity. Bees infected with Israeli acute paralysis virus and provided KATP channel activators had similar mortality rates as uninfected bees. Furthermore, we show that generation of reactive oxygen species (ROS) and regulation of ROS concentrations through pharmacological activation of KATP channels can stimulate antiviral responses, highlighting a functional framework for physiological regulation of the bee immune system. Next, we tested the influence of pharmacological activation of KATP channels on infection of 6 viruses at the colony level in the field. Data strongly support that KATP channels are a field-relevant target site as colonies treated with pinacidil, a KATP channel activator, had reduced titers of seven bee-relevant viruses by up to 75-fold and reduced them to levels comparable to non-inoculated colonies. Together, these data indicate a functional linkage between KATP channels, ROS, and antiviral defense mechanisms in bees and define a toxicologically relevant pathway that can be used for novel therapeutics development to enhance bee health and colony sustainability in the field.https://doi.org/10.1186/s12985-023-02104-0KirHoney beeReactive oxygen speciesIAPVHoney bee virusAntiviral immunity
spellingShingle Christopher J. Fellows
Michael Simone-Finstrom
Troy D. Anderson
Daniel R. Swale
Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
Virology Journal
Kir
Honey bee
Reactive oxygen species
IAPV
Honey bee virus
Antiviral immunity
title Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
title_full Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
title_fullStr Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
title_full_unstemmed Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
title_short Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
title_sort potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
topic Kir
Honey bee
Reactive oxygen species
IAPV
Honey bee virus
Antiviral immunity
url https://doi.org/10.1186/s12985-023-02104-0
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