engleski

Towards a better understanding of virus–host interplay: transcriptomic analysis of MCMV infection

Human cytomegalovirus (HCMV), a wide-spread member of the Betaherpesvirinae subfamily, is capable of establishing lifelong persistence with minimal or no damage to its host. However, in immunosuppressed and immunologically immature patients it can cause grave disease and even death. Unfortunately, the pathogenesis of HCMV infection is still poorly understood and better treatments and an effective vaccine is needed. Murine cytomegalovirus (MCMV), biologically similar and genetically related to HCMV, is an excellent model for in vivo studies. To date, many genes have been characterized thanks to a plethora of deletion mutants. However, the 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. We have employed cDNA library analysis and next generation sequencing in order to characterise all of the viral transcription products that accumulate in infected cells. Similar transcriptomic analysis 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 sense-antisense pairs and detected transcription coming from regions previously designated as non coding. Taken together, these data stress out the importance of transcriptomic analysis in construction of genomic maps. In addition, our study is among the first to investigate the transcriptome of both virus and host in the course of the infection. Analysis of host responses in vivo and in vitro has a tremendeous potential to identify new biomarkers and provide new insights into global and organ-specific responses to this virus.

cytomegalovirus transcriptomics MCMV RNASeq expression

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