Sulfolobus spindle-shaped virus 1 (SSV1) is the prototype and the most characterized member of the Fuselloviridae family (1). Upon infection, this fusellovirus establish a steady lysogenic state into the host cells. In particular, one copy of the viral genome site-specifically integrates into the host genome at an arginyl-tRNA gene, whereas 4-6 copies of the viral genome are maintained as episomal DNA. SSV1 is so far the only member of the Fuselloviridae family to show an UV-inducible life cycle, indeed, its replication is strongly enhanced by UV-light irradiation (1). The physical map of all the SSV1 transcripts (T1-9, Tx and Tind) has been determined (2) and their expression profile has been investigated before and after UV-irradiation (3), Nevertheless, the molecular mechanisms underpinning the regulation of the viral life cycle are still poorly understood. Recently, a genome-wide microarray analysis led to the identification of a novel SSV1 transcript expressed in the lysogenic host cells and termed Tlys (4). This transcript is expressed from a region lying nearby the UV-inducible Tind, whose expression is, in turn, shut off in lysogenic cells. Interestingly, Tlys encodes for a 6.3-kDa protein (F55) which has been predicted to adopt the Ribbon-Helix-Helix fold (RHH). This fold is a hallmark of negative transcription regulators that forms two-fold symmetric dimers (RHH)2 capable to bind at multiple operators arranged as inverted or tandem repeats. Noteworthy, tandem-repeated sequences have been identified in the promoters of T5, T6, Tind and Tlys transcripts. EMSA assays confirmed that F55 is able to bind these targets showing a concentration-dependent affinity, which reflects their sequence conservation in respect of a consensus. In particular, F55 showed high affinity towards targets of T5 and T6 that are overall identical to the consensus, whilst displayed a lower affinity for the target of Tind and Tlys. Consequently, a regulation mode for F55 has been proposed to explain its involvement in controlling the SSV1 lysogeny (4) Chromatin immunoprecipitation assays (ChIP) confirmed the in vivo interaction of F55 with these regulative sequences in SSV1-lysogenic cells. Moreover, it has been revealed that, soon after the UV irradiation, an apparent degradation of Tlys is induced and a consequently drop in the F55 concentration has been observed. This is consistent with the dissociation this regulator from its relative targets, thus allowing the expression of the UV-inducible transcript Tind as well as of the early transcripts T5 and T6. The physiological role of F55 in the maintenance of the SSV1 lysogeny will be discussed. References: 1. Martin A., (1984) EMBO J. 3, 2165-2168. 2. Reiter W.D., (1987) Mol Gen Genet 209, 270-275. 3. Fröls S., (2007) Virology 365, 48-59. 4. Fusco S., et al. (2013) J. Virol 87(10):5926-36
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