engleski

A Transcriptomic Approach to Viral Disease Research – MCMV transcriptome reveals unexpected genome complexity

Human cytomegalovirus (HCMV), a member of beta-herpesvirus family, is widely distributed throughout world populations. After mostly asymptomatic infection HCMV establishes a life-long persistence with minimal or no damage to its host. However, in immunosuppressed and immunologically immature patients it can cause grave disease and even death. Pathogenesis of HCMV infection is still poorly understood, there are no effective vaccines and HCMV research is hindered by its species specificity which prevents the use of animal models. Murine cytomegalovirus (MCMV) is biologically similar and genetically related and to HCMV which makes it an excellent model for studies. However, currently used genomic map of the MCMV relies heavily on ORFs predicted using bioinformatics tools and verified by genomic tilling arrays. Such analyses can miss certain ORFs, rare alternative splicing sites and do not give information about the exact 5’ and 3’ ends of the transcripts. Therefore, the goal of this project was to characterize all of the viral transcription products that accumulate in infected cells, both polyadenylated and non-polyadenylated. Similar transcriptomic analysis of just poly(A) transcripts in HCMV revealed many novel genes and gene products, and our analysis of MCMV’s transcriptome, reveals unexpected complexity of the MCMV genome which could not have been envisioned with ORF prediction software alone. We have detected a number of new transcripts and novel splice-variants, along with several S-AS pairs. Further analysis of these gene products may yield new insights into CMV diseases and represent novel treatment targets. We are in the process of generating rationally-designed gene arrays to investigate involvement and regulation of these gene products in various tissues and organs and during different infection conditions. Finally, in collaboration with IT researchers, we will integrate our data with bioinformatic tools in order to develop a publicly accessible database of the CMV transcriptome. We envision this database to serve as the definitive resource for the worldwide research community.

transcriptomics; MCMV; antisense transcription

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