Cpr1 cyclophilin and Ess1 parvulin prolyl isomerases interact with the tombusvirus replication protein and inhibit viral replication in yeast model host

Venugopal Mendu, Menghsuen Chiu, Daniel Barajas, Zhenghe Li, Peter D. Nagy

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

To identify host proteins interacting with the membrane-bound replication proteins of tombusviruses, we performed membrane yeast two-hybrid (MYTH) screens based on yeast cDNA libraries. The screens led to the identification of 57 yeast proteins interacting with replication proteins of two tombusviruses. Results from a split ubiquitin assay with 12 full-length yeast proteins and the viral replication proteins suggested that the replication proteins of two tombusviruses interact with a similar set of host proteins. Follow-up experiments with the yeast Cpr1p cyclophilin, which has prolyl isomerase activity that catalyzes cis-trans isomerization of peptidyl-prolyl bonds, confirmed that Cpr1p interacted with the viral p33 replication protein in yeast and in vitro. Replication of Tomato bushy stunt virus replicon RNA increased in cpr1δ yeast, while over-expression of Cpr1p decreased viral replication. We also show that the Ess1p parvulin prolyl isomerase partly complements Cpr1p function as an inhibitor of tombusvirus replication.

Original languageEnglish
Pages (from-to)342-351
Number of pages10
JournalVirology
Volume406
Issue number2
DOIs
StatePublished - Oct 2010

Bibliographical note

Funding Information:
We thank Dr. Judit Pogany for critical reading of the manuscript and for very helpful suggestions. The authors thank Dr. Stagjlar (U. Toronto) for yeast strains, plasmids and NubG-x and x-NubG cDNA libraries. Plasmid pHisGBK-CUP1::His33-ADH::DI72 was generated by Dr. Muhammad Shah Nawaz. This work was supported by NIH-NIAID and by the Kentucky Tobacco Research and Development Center at the University of Kentucky , awarded to PDN. Dr. Barajas was supported in part by a postdoctoral fellowship from the Spanish Ministry of Education and Science .

Keywords

  • Antiviral activity
  • Cyclophilin
  • Host factor
  • RNA replication
  • Tomato bushy stunt virus
  • Tombusvirus
  • Yeast

ASJC Scopus subject areas

  • Virology

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