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A novel role of SIRT1 in gammaherpesvirus latency and replication

Meilan He1, Shou-Jiang Gao

  • 1a Department of Molecular Microbiology and Immunology; Keck School of Medicine ; University of Southern California ; Los Angeles , CA , USA.

Cell Cycle (Georgetown, Tex.)
|December 9, 2014
PubMed

Insights

SIRT1, a metabolic sensor, inhibits Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication by silencing the RTA gene. Suppressing SIRT1 reactivates KSHV, revealing its role in viral latency.

Area of Science:

  • Virology
  • Epigenetics
  • Molecular Biology

Background:

  • Viruses manipulate host cell functions for replication.
  • SIRT1 is a key metabolic sensor and transcriptional regulator involved in cellular processes.
  • The role of SIRT1 in viral life cycles is largely unknown.

Purpose of the Study:

  • To investigate the role of SIRT1 in the life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV).
  • To determine if SIRT1 influences KSHV latency and lytic replication.

Main Methods:

  • Investigated SIRT1 binding to the KSHV RTA promoter.
  • Assessed the impact of SIRT1 inhibition or knockdown on KSHV lytic replication.
  • Analyzed changes in histone modifications (H3K4me3, H3K27me3) at the RTA promoter.
  • Examined SIRT1 interaction with KSHV RTA and its effect on transactivation.

Main Results:

  • SIRT1 binds to and silences the KSHV RTA promoter, inhibiting viral lytic replication.
  • Chemical inhibition or knockdown of SIRT1 reactivates KSHV lytic replication.
  • SIRT1 regulates KSHV latency by modulating epigenetic marks (H3K4me3, H3K27me3) at the RTA promoter.
  • SIRT1 interacts with RTA, inhibiting its transactivation activity.

Conclusions:

  • SIRT1 plays a critical role in maintaining KSHV latency by suppressing viral lytic replication.
  • SIRT1 acts as a regulator of KSHV life cycle through epigenetic mechanisms and direct interaction with viral proteins.
  • This study links the metabolic sensor SIRT1 to the regulation of gammaherpesvirus latency.
Keywords:
EpigeneticsH3K4me3 and H3K27me3KSHV Latency and ReactivationKaposi's SarcomaKaposi's Sarcoma-Associated Herpesvirus (KSHV)MetabolismNicotinamidePrimary effusion lymphomaSIRT1

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