التفاصيل البيبلوغرافية
| العنوان: |
Kv1.3-induced hyperpolarization is required for efficient Kaposi's sarcoma–associated herpesvirus lytic replication. |
| المؤلفون: |
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 |
| المصدر: |
Science Signaling; 7/16/2024, Vol. 17 Issue 845, p1-11, 11p |
| مصطلحات موضوعية: |
KAPOSI'S sarcoma-associated herpesvirus, POTASSIUM channels, B cells, T cells, KAPOSI'S sarcoma, GENE silencing, LATENT infection, GENETIC transcription |
| مستخلص: |
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. Editor's summary: Kaposi's sarcoma is driven by Kaposi's sarcoma–associated herpesvirus (KSHV), which preferentially infects B cells. Carden et al. identified a role for the voltage-gated K+ channel Kv1.3 in B cells in the lytic phase of KSHV, during which active viral replication occurs. KSHV increased the abundance and activity of Kv1.3 channels during lytic replication. Overexpression of the KSHV-encoded early protein RTA was sufficient to induce the transcription of Kv1.3-encoding mRNA. Kv1.3 maintained a hyperpolarized membrane potential that allowed Ca2+ influx, which was required for KSHV lytic replication. These results suggest that Kv1.3 is a potential target in treating KSHV-driven malignancies. —Amy E. Baek [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
