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Kv1.3-induced hyperpolarization is required for efficient Kaposi's sarcoma-associated herpesvirus lytic replication.
Carden, Holli; Harper, Katherine L; Mottram, Timothy J; Manners, Oliver; Allott, Katie L; Dallas, Mark L; Hughes, David J; Lippiat, Jonathan D; Mankouri, Jamel; Whitehouse, Adrian.
Afiliación
  • Carden H; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT Leeds, UK.
  • Harper KL; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT Leeds, UK.
  • Mottram TJ; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT Leeds, UK.
  • Manners O; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT Leeds, UK.
  • Allott KL; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT Leeds, UK.
  • Dallas ML; School of Pharmacy, University of Reading, RG6 6AP Reading, UK.
  • Hughes DJ; Biomedical Sciences Research Complex, School of Biology, University of St Andrews, North Haugh, KY16 9ST St Andrews, UK.
  • Lippiat JD; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, LS2 9JT Leeds, UK.
  • Mankouri J; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT Leeds, UK.
  • Whitehouse A; School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT Leeds, UK.
Sci Signal ; 17(845): eadg4124, 2024 07 16.
Article en En | MEDLINE | ID: mdl-39012937
ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked directly to the development of Kaposi's sarcoma. KSHV establishes a latent infection in B cells, which can be reactivated to initiate lytic replication, producing infectious virions. Using pharmacological and genetic silencing approaches, we showed that the voltage-gated K+ channel Kv1.3 in B cells enhanced KSHV lytic replication. The KSHV replication and transcription activator (RTA) protein increased the abundance of Kv1.3 and led to enhanced K+ channel activity and hyperpolarization of the B cell membrane. Enhanced Kv1.3 activity promoted intracellular Ca2+ influx, leading to the Ca2+-driven nuclear localization of KSHV RTA and host nuclear factor of activated T cells (NFAT) proteins and subsequently increased the expression of NFAT1 target genes. KSHV lytic replication and infectious virion production were inhibited by Kv1.3 blockers or silencing. These findings highlight Kv1.3 as a druggable host factor that is key to the successful completion of KSHV lytic replication.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación Viral / Herpesvirus Humano 8 / Canal de Potasio Kv1.3 / Factores de Transcripción NFATC Límite: Humans Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación Viral / Herpesvirus Humano 8 / Canal de Potasio Kv1.3 / Factores de Transcripción NFATC Límite: Humans Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos