The TPR domain in the host Cyp40-like cyclophilin binds to the viral replication protein and inhibits the assembly of the tombusviral replicase

Jing Yi Lin, Venugopal Mendu, Judit Pogany, Jun Qin, Peter D. Nagy

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Replication of plus-stranded RNA viruses is greatly affected by numerous host-coded proteins acting either as susceptibility or resistance factors. Previous genome-wide screens and global proteomics approaches with Tomato bushy stunt tombusvirus (TBSV) in a yeast model host revealed the involvement of cyclophilins, which are a large family of host prolyl isomerases, in TBSV replication. In this paper, we identified those members of the large cyclophilin family that interacted with the viral replication proteins and inhibited TBSV replication. Further characterization of the most effective cyclophilin, the Cyp40-like Cpr7p, revealed that it strongly inhibits many steps during TBSV replication in a cell-free replication assay. These steps include viral RNA recruitment inhibited via binding of Cpr7p to the RNA-binding region of the viral replication protein; the assembly of the viral replicase complex and viral RNA synthesis. Since the TPR (tetratricopeptide repeats) domain, but not the catalytic domain of Cpr7p is needed for the inhibitory effect on TBSV replication, it seems that the chaperone activity of Cpr7p provides the negative regulatory function. We also show that three Cyp40-like proteins from plants can inhibit TBSV replication in vitro and Cpr7p is also effective against Nodamura virus, an insect pathogen. Overall, the current work revealed a role for Cyp40-like proteins and their TPR domains as regulators of RNA virus replication.

Original languageEnglish
Article numbere1002491
JournalPLoS Pathogens
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 2012
Externally publishedYes

Fingerprint

Tombusvirus
Cyclophilins
Viral Proteins
RNA Viruses
Viral RNA
Insect Viruses
Peptidylprolyl Isomerase
Virus Assembly
Plant Proteins
R Factors
Lycopersicon esculentum
Virus Replication
Proteomics
Catalytic Domain
Proteins
Yeasts
Genome
RNA

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

The TPR domain in the host Cyp40-like cyclophilin binds to the viral replication protein and inhibits the assembly of the tombusviral replicase. / Lin, Jing Yi; Mendu, Venugopal; Pogany, Judit; Qin, Jun; Nagy, Peter D.

In: PLoS Pathogens, Vol. 8, No. 2, e1002491, 02.2012.

Research output: Contribution to journalArticle

Lin, Jing Yi ; Mendu, Venugopal ; Pogany, Judit ; Qin, Jun ; Nagy, Peter D. / The TPR domain in the host Cyp40-like cyclophilin binds to the viral replication protein and inhibits the assembly of the tombusviral replicase. In: PLoS Pathogens. 2012 ; Vol. 8, No. 2.
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