This Article Full Text Full Text (PDF) An erratum has been published Other Versions of this Article: JVI.01101-07v1 81/21/11917    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zheng, H. Articles by Zhou, X. Search for Related Content PubMed PubMed Citation Articles by Zheng, H. Articles by Zhou, X.

Torque Teno Virus (SANBAN Isolate) ORF2 Protein Suppresses NF-B Pathways via Interaction with IB Kinases

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072 China

Received 22 May 2007/ Accepted 31 July 2007

Since the first discovery of Torque teno virus (TTV) in 1997, many researchers focused on its epidemiology and transcriptional regulation, but the function of TTV-encoded proteins remained unknown. The function of the TTV open reading frame (ORF) in the nuclear factor B (NF-B) pathway has not yet been established. In this study, we found for the first time that the TTV ORF2 protein could suppress NF-B activity in a dose-dependent manner in the canonical NF-B pathway. By Western blot analysis, we proved that the TTV ORF2 protein did not alter the level of NF-B expression but prevented the p50 and p65 subunits from entering the nucleus due to the inhibition of IB protein degradation. Further immunoprecipitation assays showed that the TTV ORF2 protein could physically interact with IKKß as well as IKK, but not IKK. Luciferase assays and Western blot experiments showed that the TTV ORF2 protein could also suppress NF-B activity in the noncanonical NF-B pathway and block the activation and translocation of p52. Finally, we found that the TTV ORF2 protein inhibited the transcription of NF-B-mediated downstream genes (interleukin 6 [IL-6], IL-8, and COX-2) through down-regulation of NF-B. Together, these data indicate that the TTV ORF2 protein suppresses the canonical and noncanonical NF-B pathways, suggesting that the TTV ORF2 protein may be involved in regulating the innate and adaptive immunity of organisms, contributing to TTV pathogenesis, and even be related to some diseases.

Published ahead of print on 8 August 2007.