The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus inhibits expression of SUMO/sentrin-specific peptidase 6 to facilitate establishment of latency

Xiaoxi Lin, Rui Sun, Fang Zhang, Yuan Gao, Lianghua Bin, Ke Lan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV), which belongs to the Gammaherpesviridae, typically displays two different phases in its life cycle, the latent phase and the lytic phase. Latency-associated nuclear antigen (LANA), the primary viral product during latency, has been reported to bind to a series of cellular gene promoters to modulate gene transcription. To systemically elucidate the cellular genes regulated by LANA, we identified genome-wide LANA binding sites by chromatin immunoprecipitation coupled with sequencing (ChIP-seq). We stratified ChIP-seq data and found that LANA might be involved in the macromolecule catabolic process. Specifically, we found and verified that LANA could directly bind to the promoter of the SUMO/sentrin-specific peptidase 6 (SENP6) gene in vivo and in vitro. LANA could repress SENP6 promoter activity in a dose-dependent manner in a reporter gene assay. LANA expression was sufficient to inhibit endogenous SENP6 expression at both the RNA and protein levels. Moreover, SENP6 overexpression in KSHV-infected cells reduced LANA at the protein level. Mechanistically, we found that SENP6 could interact with LANA and reduce the formation of sumoylated LANA, which relies on the desumoylation ability of SENP6. During de novo infection, SENP6 overexpression would decrease the abundance of LANA and enhance viral gene expression, which would hamper the establishment of latency. Taken together, these data suggest that KSHV-encoded LANA could inhibit SENP6 expression to regulate the abundance of itself, which may play an important role in controlling the establishment of latency.

Original languageEnglish
Article numbere00806-17
JournalJournal of Virology
Volume91
Issue number17
DOIs
StatePublished - 1 Sep 2017
Externally publishedYes

Keywords

  • ChIP-seq
  • KSHV
  • Kaposi's sarcoma-associated herpesvirus
  • LANA
  • SENP6
  • Sumoylation

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