Important role of N108 residue in binding of bovine foamy virus transactivator Tas to viral promoters
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RESEARCH
Open Access
Important role of N108 residue in binding of bovine foamy virus transactivator Tas to viral promoters Tiejun Bing†, Suzhen Zhang†, Xiaojuan Liu, Zhibin Liang, Peng Shao, Song Zhang, Wentao Qiao and Juan Tan*
Abstract Background: Bovine foamy virus (BFV) encodes the transactivator BTas, which enhances viral gene transcription by binding to the long terminal repeat promoter and the internal promoter. In this study, we investigated the different replication capacities of two similar BFV full-length DNA clones, pBS-BFV-Y and pBS-BFV-B. Results: Here, functional analysis of several chimeric clones revealed a major role for the C-terminal region of the viral genome in causing this difference. Furthermore, BTas-B, which is located in this C-terminal region, exhibited a 20-fold higher transactivation activity than BTas-Y. Sequence alignment showed that these two sequences differ only at amino acid 108, with BTas-B containing N108 and BTas-Y containing D108 at this position. Results of mutagenesis studies demonstrated that residue N108 is important for BTas binding to viral promoters. In addition, the N108D mutation in pBS-BFV-B reduced the viral replication capacity by about 1.5-fold. Conclusions: Our results suggest that residue N108 is important for BTas binding to BFV promoters and has a major role in BFV replication. These findings not only advances our understanding of the transactivation mechanism of BTas, but they also highlight the importance of certain sequence polymorphisms in modulating the replication capacity of isolated BFV clones. Keywords: Bovine foamy virus, Infectious clone, BTas, Promoter
Background Foamy viruses (FVs) form the only genus in the Spumaretrovirinae subfamily of the Retroviridae family and are widespread in various animals, including simian [1, 2], bovine [3], equine [4] and feline [5] species. FVs have extensive cellular tropism and can infect many different kinds of cells resulting in lytic replication (Cf2Th cells and BHK-21 cells) or persistence (HEK293T cells and HeLa cells). However, FVs are nonpathogenic in their natural hosts or in experimentally infected animals. The genomic nature, replication strategy, and gene expression of FVs are different in many aspects from other retroviruses. The replication of FVs genes is dependent on two distinct promoters: the 5’ long terminal repeat (LTR) regulates the expression of three structural genes (gag, pol and env), and an internal promoter (IP) located * Correspondence: [email protected] † Equal contributors Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
between the env gene and the 3’ LTR also regulates the expression of two regulatory genes (tas and bet). Tas, a transcriptional transactivator, is essential for FV replication. The Tas protein binds directly to a DNA sequence in the viral LTR promoter and IP to enhance viral gene transcription [6–10]. Nuclear localization of the prototype FV (PFV) Tas is essential
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