The FAT10 posttranslational modification is involved in lytic replication of kaposi's sarcoma-associated herpesvirus

Atsuko Sugimoto, Yuichi Abe, Tadashi Watanabe, Kohei Hosokawa, Jun Adachi, Takeshi Tomonaga, Yasumasa Iwatani, Takayuki Murata, Masahiro Fujimuro

研究成果: Article査読

抄録

During Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication, host cell functions, including protein expression and posttranslational modification pathways, are dysregulated by KSHV to promote virus production. Here, we attempted to identify key proteins for KSHV lytic replication by profiling protein expression in the latent and lytic phases using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteomic analysis, immunoblotting, and quantitative PCR demonstrated that antigen F (HLA-F) adjacent transcript 10 (FAT10) and UBE1L2 (also known as ubiquitin-like modifier-activating enzyme 6 [UBA6]) were upregulated during lytic replication. FAT10 is a ubiquitin-like protein (UBL). UBE1L2 is the FAT10-activating enzyme (E1), which is essential for FAT10 modification (FAT10ylation). FAT10ylated proteins were immediately expressed after lytic induction and increased over time during lytic replication. Knockout of UBE1L2 suppressed KSHV production but not KSHV DNA synthesis. In order to isolate FAT10ylated proteins during KSHV lytic replication, we conducted immunoprecipitation using anti-FAT10 antibody and nickel-nitrilotriacetic acid (Ni-NTA) chromatography of exogenously expressed His-tagged FAT10 from cells undergoing latent or lytic replication. LC-MS/MS was performed to identify FAT10ylated proteins. We identified KSHV ORF59 and ORF61 as FAT10ylation substrates. Our study revealed that the UBE1L2-FAT10 system is upregulated during KSHV lytic replication, and it contributes to viral propagation.

本文言語English
論文番号e02194-20
ジャーナルJournal of Virology
95
10
DOI
出版ステータスPublished - 05-2021

All Science Journal Classification (ASJC) codes

  • 微生物学
  • 免疫学
  • 昆虫科学
  • ウイルス学

フィンガープリント

「The FAT10 posttranslational modification is involved in lytic replication of kaposi's sarcoma-associated herpesvirus」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル