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Cellular endosomal potassium ion flux regulates arenavirus uncoating during virus entry
Cellular endosomal potassium ion flux regulates arenavirus uncoating during virus entry
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Length:
20 minutes
Released:
Jun 26, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.06.23.546275v1?rss=1
Authors: Shaw, A. B., Tse, H. N., Byford, O., plahe, g., Moon-Walker, A., Saphire, E. O., Whelan, S. P. J., Mankouri, J., Fontana, J., Barr, J. N.
Abstract:
Lymphocytic choriomeningitis virus (LCMV) is a model arenavirus that causes fatalities within immunocompromised populations. To enter cells, the LCMV envelope fuses with endosomal membranes, for which two requirements are low pH and interaction between LCMV GP spike and receptor CD164. LCMV subsequently uncoats, where genome-associated NP separates from Z matrix. To further examine LCMV entry, an siRNA screen identified K+ channels as important for LCMV infection, and pharmacological inhibition confirmed K+ involvement during entry. We tracked incoming virions along their entry pathway under physiological conditions, where uncoating was signified by separation of NP and Z. In contrast, K+ channel blockade, prevented uncoating, trapping virions within Rab7 and CD164-positive endosomes, identifying K+ as a third LCMV entry requirement. K+ did not increase GP/CD164 binding, thus we suggest K+ mediates uncoating by modulating NP/Z interactions within the virion interior. These results suggest repurposing licensed K+ channel inhibitors represents a potential anti-arenaviral strategy.
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http://biorxiv.org/cgi/content/short/2023.06.23.546275v1?rss=1
Authors: Shaw, A. B., Tse, H. N., Byford, O., plahe, g., Moon-Walker, A., Saphire, E. O., Whelan, S. P. J., Mankouri, J., Fontana, J., Barr, J. N.
Abstract:
Lymphocytic choriomeningitis virus (LCMV) is a model arenavirus that causes fatalities within immunocompromised populations. To enter cells, the LCMV envelope fuses with endosomal membranes, for which two requirements are low pH and interaction between LCMV GP spike and receptor CD164. LCMV subsequently uncoats, where genome-associated NP separates from Z matrix. To further examine LCMV entry, an siRNA screen identified K+ channels as important for LCMV infection, and pharmacological inhibition confirmed K+ involvement during entry. We tracked incoming virions along their entry pathway under physiological conditions, where uncoating was signified by separation of NP and Z. In contrast, K+ channel blockade, prevented uncoating, trapping virions within Rab7 and CD164-positive endosomes, identifying K+ as a third LCMV entry requirement. K+ did not increase GP/CD164 binding, thus we suggest K+ mediates uncoating by modulating NP/Z interactions within the virion interior. These results suggest repurposing licensed K+ channel inhibitors represents a potential anti-arenaviral strategy.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Jun 26, 2023
Format:
Podcast episode
Titles in the series (100)
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