The Hop-like stress-induced protein 1 cochaperone is a novel cell-intrinsic restriction factor for mitochondrial tombusvirus replication

Kai Xu, Jing Yi Lin, Peter D. Nagy

研究成果: 雜誌貢獻文章同行評審

18 引文 斯高帕斯(Scopus)

摘要

Recent genome-wide screens reveal that the host cells express an arsenal of proteins that inhibit replication of plus-stranded RNA viruses by functioning as cell-intrinsic restriction factors of viral infections. One group of cell-intrinsic restriction factors against tombusviruses contains tetratricopeptide repeat (TPR) domains that directly interact with the viral replication proteins. In this paper, we find that the TPR domain-containing Hop-like stress-inducible protein 1 (Sti1p) cochaperone selectively inhibits the mitochondrial membrane-based replication of Carnation Italian ringspot tombusvirus (CIRV). In contrast, Sti1/Hop does not inhibit the peroxisome membrane-based replication of the closely related Tomato bushy stunt virus (TBSV) or Cucumber necrosis virus (CNV) in a yeast model or in plants. Deletion of STI1 in yeast leads to up to a 4-fold increase in CIRV replication, and knockdown of the orthologous Hop cochaperone in plants results in a 3-fold increase in CIRV accumulation. Overexpression of Sti1p derivatives in yeast reveals that the inhibitory function depends on the TPR1 domain known to interact with heat shock protein 70 (Hsp70), but not on the TPR2 domain interacting with Hsp90. In vitro CIRV replication studies based on isolated mitochondrial preparations and purified recombinant proteins has confirmed that Sti1p, similar to the TPR-containing Cyp40-like Cpr7p cyclophilin and the Ttc4 oncogene-like Cns1 cochaperone, is a strong inhibitor of CIRV replication. Sti1p interacts and colocalizes with the CIRV replication proteins in yeast. Our findings indicate that the TPR-containing Hop/Sti1 cochaperone could act as a cell-intrinsic virus restriction factor of the mitochondrial CIRV, but not against the peroxisomal tombusviruses in yeast and plants.

原文英語
頁(從 - 到)9361-9378
頁數18
期刊Journal of Virology
88
發行號16
DOIs
出版狀態已發佈 - 2014

ASJC Scopus subject areas

  • 微生物學
  • 免疫學
  • 昆蟲科學
  • 病毒學

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