Host microRNA-31-5p represses oncogenic herpesvirus lytic reactivation by restricting the RNA-binding protein KHDRBS3-mediated viral gene expression DOI Open Access
Soo Mi Lee,

Christopher L. Avalos,

Christos Miliotis

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), an etiological agent of sarcoma and primary effusion lymphoma, employs a biphasic life cycle consisting latency lytic replication to achieve lifelong infection. Despite its essential role in KSHV persistence tumorigenicity, much remains unknown about how reactivation is regulated. Leveraging high-throughput transcriptomics, we identify microRNA-31-5p (miR-31-5p) as key regulator capable restricting entry into the cycle. Ectopic expression miR-31-5p impairs gene transcription production viral proteins, culminating dramatic reduction infectious virion during reactivation. overexpression also markedly reduces critical early genes, including master latent-lytic switch, activator (RTA) protein. Through mechanistic studies, demonstrate that represses by directly targeting KH domain protein KHDRBS3, RNA-binding known regulate RNA processing alternative splicing. Our study highlights KHDRBS3 proviral host factor successful completion suggests novel function Taken together, these findings reveal previously unrecognized for miR-31-5p/KHDRBS3 axis regulating latency-lytic switch provide insights regulation KSHV, which may be leveraged cycle-targeted therapeutic strategies against KSHV-associated malignancies.

Language: Английский

Host microRNA-31-5p represses oncogenic herpesvirus lytic reactivation by restricting the RNA-binding protein KHDRBS3-mediated viral gene expression DOI Open Access
Soo Mi Lee,

Christopher L. Avalos,

Christos Miliotis

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), an etiological agent of sarcoma and primary effusion lymphoma, employs a biphasic life cycle consisting latency lytic replication to achieve lifelong infection. Despite its essential role in KSHV persistence tumorigenicity, much remains unknown about how reactivation is regulated. Leveraging high-throughput transcriptomics, we identify microRNA-31-5p (miR-31-5p) as key regulator capable restricting entry into the cycle. Ectopic expression miR-31-5p impairs gene transcription production viral proteins, culminating dramatic reduction infectious virion during reactivation. overexpression also markedly reduces critical early genes, including master latent-lytic switch, activator (RTA) protein. Through mechanistic studies, demonstrate that represses by directly targeting KH domain protein KHDRBS3, RNA-binding known regulate RNA processing alternative splicing. Our study highlights KHDRBS3 proviral host factor successful completion suggests novel function Taken together, these findings reveal previously unrecognized for miR-31-5p/KHDRBS3 axis regulating latency-lytic switch provide insights regulation KSHV, which may be leveraged cycle-targeted therapeutic strategies against KSHV-associated malignancies.

Language: Английский

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