engleski

MCMV encoded highly abundant transcript with several coding, non-coding and immune-evasive roles

Recent advances in sequencing technology enabled us to perform comprehensive transcriptomic profiling of MCMV infection of MEFs and demonstrate that transcriptional profile and coding potential of herpesviruses have a much greater complexity than previously anticipated. Our analysis identified numerous novel spliced and unspliced MCMV transcripts, among which the most abundant viral transcripts are novel transcripts of unknown function. Among these, MAT (Most Abundant Transcript) is the most highly expressed throughout the infection. It has been shown earlier that MAT encodes a protein (Juranic Lisnic et al (2013) PLOS Pathogens) and contains a binding site for cellular microRNA miR-27 (Marcinowski et al (2012) PLOS Pathogens), making it a first reported viral transcript with coding and non-coding functions. We have recently detected an additional protein encoded by this enigmatic transcript, and here we report that deletion of the MCMV genomic region encoding MAT results in attenuation of the virus in vivo. However, the underlying mechanisms are not completely elucidated due to multiple functions MAT performs in the infected cells. On one hand, MAT deficiency results in failure to deplete cellular levels of miR-27, an important regulator of cell-cycle, while on the other MAT deletion mutants evade the detection by NK cells through activating Ly49 receptors P, L and D2. We also show that absence of MAT results in dramatic changes of host and viral peptides presented in the context of MHC I. In conclusion, not only does MAT provide an excellent example of the complex regulatory potential of herpesviral genes, where single transcripts exerts numerous and diverse functions, it also raises the question of how many new herpesviral genes, especially immune evasion genes, remain to be discovered.

cmv; cytomegalovirus; NK cells; Ly49; m04; MAT

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